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Challenges in trancorneal drug
delivery
Presented by
Bibin Mathew
MPharm IP(2nd Sem)
Introduction
Ocular pharmacokinetics
Pathway of the drug after instillation
Challenges related to routes of administration
Barriers to drug absorption
Conventional ocular drug delivery constraints
Nasolacrimal drainage
Approaches to overcome constraints of conventional dosage form
Novel ocular drug delivery
Marketed formulations
Conclusion
Medication is applied to the surface of the eye for two purposes
diams To treat the surface of eye
diams To provide intraocular treatment
90 ocular market conventional dosage form
5 of applied drug penetrates
Major challenge remains to past the protective ocular
barriers
Good corneal penetration
Prolong contact time with corneal tissue
Simplicity of instillation for the patient
Non irritative and comfortable form
Appropriate rheological properties
Ocular pharmacokinetics
Ocular structure with routes of drug kinetics
Systemic administration
Limited penetration potential systemic
toxicity
Intraocular implants
Increased risk of retinal detachment and
intravitrealhemorrahge
Intravitreal injections
Increased risk of retinal detachment hemorrhage
and catracts
Topical application
Limited penetration (5) rapid tear
washout poor patient compliance
Flow of lacrimal fluid removes instilledcompounds from the surface of eye
Excess volume is flown to thenasolacrimal duct rapidly
Corneal barrier is formed uponmaturation of epithelial cells
Most apical corneal epithelial cells fromtight junctions that limit the paracellulardrug permeation
These barriers have two parts
Blood retina barrier
Blood-aqueous barrier
Volume
Lacrimation
Tear dilution
Blinking
BARRIERS
Drug loss from ocular surface Lacrimal fluid eye barrier
Blood ocular barriers Others
CORNEL AREA
Drug interaction
Drug protein interaction
Instilled dose
Corneal absorption
Normal tear turn overInduced lacrimation
Conjunctival absorption
Consists of a secretory distributive and collection part
Secretory portion composed of the lacrimalgland Tears are spread over the ocular surfaceby the eyelids during blinking
Collecting system consists of the canaliculithe lacrimal sac the nasolacrimal duct whichhas opening in the inferior
The basal tear flow is of about 12 microlmin(range 05ndash22 microlmin) Reflex stimulationmay increase lacrimation a hundred-fold times
Nasolacrimal drainage
Attainment of optimaldrug concentration
Enhance the poor bioavailability of drugs
To increase bioavailability and duration of ocular
drugs
Use of DDS which provide the controlled and continuous delivery
Maximizing corneal drug absorption and minimizing precorneal drug loss
1Viscosity enhancers
Solution Viscosity Solution Drainage
Enhances viscosity of the formulation
Slows elimination rate from the precorneal area and enhance contact time
Generally hydrophilic polymers- e Methyl cellulose polyvinyl alcohols
polyacrylic acids sodium carboxy methyl cellulose etc
A minimum viscosity of 20 cSt is needed for optimum corneal absorption
Approaches to overcome constraints of
conventional dosage form
2 Prodrugs
Prodrugs enhance corneal drug permeability through modification of the
hydrophilic or lipophilicity of the drug
The method includes modification of chemical structure of the drug molecule
thus making it selective site specific and a safe ocular drug delivery system
Drugs with increased penetrability through prodrug formulations are
epinehrine phenylephrine timolol pilocarpine
Dipivefrine prodrug of epinephrine has 17 times better ability to penetrate
across the cornea Thus is because dipivefrine is 600times more lipophilic
(at pH 72) than epinephrine
Phenylephrine hydrochloride prodrug of phenylephrine raised the amount
of phenylephrine in the aqueous humor by 6-8 times and improved
mydriatic activity four fold
Poor aqueous stability
Post aqueous solubility
Eye irritation
Polymereric mucoadhesive vehicle retained in the eye due to non-
covalent bonding with conjuctival mucine
Mucine is capable of picking of 40-80 times of weight of water
Thus prolongs the residence time of drug in the conjuctival sac
Mucoadhesives contain the dosage form which remains adhered to
cornea until the polymer is degraded or mucus replaces itself
Types-
1) Naturally Occurring Mucoadhesives- Lectins Fibronectins
2) Synthetic Mucoadhesives-PVACarbopol carboxy methyl
cellulose cross-linked polyacrylic acid
Drugs incarporated in to this are pilocarpine lidocaine
benzocaine and prednisolone acetate
Mucoadhesives
Objectives
To reduce the frequency of administration
To provide controlled continuous drug delivery
To prolong the pre ocular retention
To avoid or minimize the initial drug concentration peak in the
aqueous humor
To avoid periods of under-dosing that may occur between eye
drop instillation
Novel ocular drug delivery system
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Introduction
Ocular pharmacokinetics
Pathway of the drug after instillation
Challenges related to routes of administration
Barriers to drug absorption
Conventional ocular drug delivery constraints
Nasolacrimal drainage
Approaches to overcome constraints of conventional dosage form
Novel ocular drug delivery
Marketed formulations
Conclusion
Medication is applied to the surface of the eye for two purposes
diams To treat the surface of eye
diams To provide intraocular treatment
90 ocular market conventional dosage form
5 of applied drug penetrates
Major challenge remains to past the protective ocular
barriers
Good corneal penetration
Prolong contact time with corneal tissue
Simplicity of instillation for the patient
Non irritative and comfortable form
Appropriate rheological properties
Ocular pharmacokinetics
Ocular structure with routes of drug kinetics
Systemic administration
Limited penetration potential systemic
toxicity
Intraocular implants
Increased risk of retinal detachment and
intravitrealhemorrahge
Intravitreal injections
Increased risk of retinal detachment hemorrhage
and catracts
Topical application
Limited penetration (5) rapid tear
washout poor patient compliance
Flow of lacrimal fluid removes instilledcompounds from the surface of eye
Excess volume is flown to thenasolacrimal duct rapidly
Corneal barrier is formed uponmaturation of epithelial cells
Most apical corneal epithelial cells fromtight junctions that limit the paracellulardrug permeation
These barriers have two parts
Blood retina barrier
Blood-aqueous barrier
Volume
Lacrimation
Tear dilution
Blinking
BARRIERS
Drug loss from ocular surface Lacrimal fluid eye barrier
Blood ocular barriers Others
CORNEL AREA
Drug interaction
Drug protein interaction
Instilled dose
Corneal absorption
Normal tear turn overInduced lacrimation
Conjunctival absorption
Consists of a secretory distributive and collection part
Secretory portion composed of the lacrimalgland Tears are spread over the ocular surfaceby the eyelids during blinking
Collecting system consists of the canaliculithe lacrimal sac the nasolacrimal duct whichhas opening in the inferior
The basal tear flow is of about 12 microlmin(range 05ndash22 microlmin) Reflex stimulationmay increase lacrimation a hundred-fold times
Nasolacrimal drainage
Attainment of optimaldrug concentration
Enhance the poor bioavailability of drugs
To increase bioavailability and duration of ocular
drugs
Use of DDS which provide the controlled and continuous delivery
Maximizing corneal drug absorption and minimizing precorneal drug loss
1Viscosity enhancers
Solution Viscosity Solution Drainage
Enhances viscosity of the formulation
Slows elimination rate from the precorneal area and enhance contact time
Generally hydrophilic polymers- e Methyl cellulose polyvinyl alcohols
polyacrylic acids sodium carboxy methyl cellulose etc
A minimum viscosity of 20 cSt is needed for optimum corneal absorption
Approaches to overcome constraints of
conventional dosage form
2 Prodrugs
Prodrugs enhance corneal drug permeability through modification of the
hydrophilic or lipophilicity of the drug
The method includes modification of chemical structure of the drug molecule
thus making it selective site specific and a safe ocular drug delivery system
Drugs with increased penetrability through prodrug formulations are
epinehrine phenylephrine timolol pilocarpine
Dipivefrine prodrug of epinephrine has 17 times better ability to penetrate
across the cornea Thus is because dipivefrine is 600times more lipophilic
(at pH 72) than epinephrine
Phenylephrine hydrochloride prodrug of phenylephrine raised the amount
of phenylephrine in the aqueous humor by 6-8 times and improved
mydriatic activity four fold
Poor aqueous stability
Post aqueous solubility
Eye irritation
Polymereric mucoadhesive vehicle retained in the eye due to non-
covalent bonding with conjuctival mucine
Mucine is capable of picking of 40-80 times of weight of water
Thus prolongs the residence time of drug in the conjuctival sac
Mucoadhesives contain the dosage form which remains adhered to
cornea until the polymer is degraded or mucus replaces itself
Types-
1) Naturally Occurring Mucoadhesives- Lectins Fibronectins
2) Synthetic Mucoadhesives-PVACarbopol carboxy methyl
cellulose cross-linked polyacrylic acid
Drugs incarporated in to this are pilocarpine lidocaine
benzocaine and prednisolone acetate
Mucoadhesives
Objectives
To reduce the frequency of administration
To provide controlled continuous drug delivery
To prolong the pre ocular retention
To avoid or minimize the initial drug concentration peak in the
aqueous humor
To avoid periods of under-dosing that may occur between eye
drop instillation
Novel ocular drug delivery system
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Medication is applied to the surface of the eye for two purposes
diams To treat the surface of eye
diams To provide intraocular treatment
90 ocular market conventional dosage form
5 of applied drug penetrates
Major challenge remains to past the protective ocular
barriers
Good corneal penetration
Prolong contact time with corneal tissue
Simplicity of instillation for the patient
Non irritative and comfortable form
Appropriate rheological properties
Ocular pharmacokinetics
Ocular structure with routes of drug kinetics
Systemic administration
Limited penetration potential systemic
toxicity
Intraocular implants
Increased risk of retinal detachment and
intravitrealhemorrahge
Intravitreal injections
Increased risk of retinal detachment hemorrhage
and catracts
Topical application
Limited penetration (5) rapid tear
washout poor patient compliance
Flow of lacrimal fluid removes instilledcompounds from the surface of eye
Excess volume is flown to thenasolacrimal duct rapidly
Corneal barrier is formed uponmaturation of epithelial cells
Most apical corneal epithelial cells fromtight junctions that limit the paracellulardrug permeation
These barriers have two parts
Blood retina barrier
Blood-aqueous barrier
Volume
Lacrimation
Tear dilution
Blinking
BARRIERS
Drug loss from ocular surface Lacrimal fluid eye barrier
Blood ocular barriers Others
CORNEL AREA
Drug interaction
Drug protein interaction
Instilled dose
Corneal absorption
Normal tear turn overInduced lacrimation
Conjunctival absorption
Consists of a secretory distributive and collection part
Secretory portion composed of the lacrimalgland Tears are spread over the ocular surfaceby the eyelids during blinking
Collecting system consists of the canaliculithe lacrimal sac the nasolacrimal duct whichhas opening in the inferior
The basal tear flow is of about 12 microlmin(range 05ndash22 microlmin) Reflex stimulationmay increase lacrimation a hundred-fold times
Nasolacrimal drainage
Attainment of optimaldrug concentration
Enhance the poor bioavailability of drugs
To increase bioavailability and duration of ocular
drugs
Use of DDS which provide the controlled and continuous delivery
Maximizing corneal drug absorption and minimizing precorneal drug loss
1Viscosity enhancers
Solution Viscosity Solution Drainage
Enhances viscosity of the formulation
Slows elimination rate from the precorneal area and enhance contact time
Generally hydrophilic polymers- e Methyl cellulose polyvinyl alcohols
polyacrylic acids sodium carboxy methyl cellulose etc
A minimum viscosity of 20 cSt is needed for optimum corneal absorption
Approaches to overcome constraints of
conventional dosage form
2 Prodrugs
Prodrugs enhance corneal drug permeability through modification of the
hydrophilic or lipophilicity of the drug
The method includes modification of chemical structure of the drug molecule
thus making it selective site specific and a safe ocular drug delivery system
Drugs with increased penetrability through prodrug formulations are
epinehrine phenylephrine timolol pilocarpine
Dipivefrine prodrug of epinephrine has 17 times better ability to penetrate
across the cornea Thus is because dipivefrine is 600times more lipophilic
(at pH 72) than epinephrine
Phenylephrine hydrochloride prodrug of phenylephrine raised the amount
of phenylephrine in the aqueous humor by 6-8 times and improved
mydriatic activity four fold
Poor aqueous stability
Post aqueous solubility
Eye irritation
Polymereric mucoadhesive vehicle retained in the eye due to non-
covalent bonding with conjuctival mucine
Mucine is capable of picking of 40-80 times of weight of water
Thus prolongs the residence time of drug in the conjuctival sac
Mucoadhesives contain the dosage form which remains adhered to
cornea until the polymer is degraded or mucus replaces itself
Types-
1) Naturally Occurring Mucoadhesives- Lectins Fibronectins
2) Synthetic Mucoadhesives-PVACarbopol carboxy methyl
cellulose cross-linked polyacrylic acid
Drugs incarporated in to this are pilocarpine lidocaine
benzocaine and prednisolone acetate
Mucoadhesives
Objectives
To reduce the frequency of administration
To provide controlled continuous drug delivery
To prolong the pre ocular retention
To avoid or minimize the initial drug concentration peak in the
aqueous humor
To avoid periods of under-dosing that may occur between eye
drop instillation
Novel ocular drug delivery system
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Good corneal penetration
Prolong contact time with corneal tissue
Simplicity of instillation for the patient
Non irritative and comfortable form
Appropriate rheological properties
Ocular pharmacokinetics
Ocular structure with routes of drug kinetics
Systemic administration
Limited penetration potential systemic
toxicity
Intraocular implants
Increased risk of retinal detachment and
intravitrealhemorrahge
Intravitreal injections
Increased risk of retinal detachment hemorrhage
and catracts
Topical application
Limited penetration (5) rapid tear
washout poor patient compliance
Flow of lacrimal fluid removes instilledcompounds from the surface of eye
Excess volume is flown to thenasolacrimal duct rapidly
Corneal barrier is formed uponmaturation of epithelial cells
Most apical corneal epithelial cells fromtight junctions that limit the paracellulardrug permeation
These barriers have two parts
Blood retina barrier
Blood-aqueous barrier
Volume
Lacrimation
Tear dilution
Blinking
BARRIERS
Drug loss from ocular surface Lacrimal fluid eye barrier
Blood ocular barriers Others
CORNEL AREA
Drug interaction
Drug protein interaction
Instilled dose
Corneal absorption
Normal tear turn overInduced lacrimation
Conjunctival absorption
Consists of a secretory distributive and collection part
Secretory portion composed of the lacrimalgland Tears are spread over the ocular surfaceby the eyelids during blinking
Collecting system consists of the canaliculithe lacrimal sac the nasolacrimal duct whichhas opening in the inferior
The basal tear flow is of about 12 microlmin(range 05ndash22 microlmin) Reflex stimulationmay increase lacrimation a hundred-fold times
Nasolacrimal drainage
Attainment of optimaldrug concentration
Enhance the poor bioavailability of drugs
To increase bioavailability and duration of ocular
drugs
Use of DDS which provide the controlled and continuous delivery
Maximizing corneal drug absorption and minimizing precorneal drug loss
1Viscosity enhancers
Solution Viscosity Solution Drainage
Enhances viscosity of the formulation
Slows elimination rate from the precorneal area and enhance contact time
Generally hydrophilic polymers- e Methyl cellulose polyvinyl alcohols
polyacrylic acids sodium carboxy methyl cellulose etc
A minimum viscosity of 20 cSt is needed for optimum corneal absorption
Approaches to overcome constraints of
conventional dosage form
2 Prodrugs
Prodrugs enhance corneal drug permeability through modification of the
hydrophilic or lipophilicity of the drug
The method includes modification of chemical structure of the drug molecule
thus making it selective site specific and a safe ocular drug delivery system
Drugs with increased penetrability through prodrug formulations are
epinehrine phenylephrine timolol pilocarpine
Dipivefrine prodrug of epinephrine has 17 times better ability to penetrate
across the cornea Thus is because dipivefrine is 600times more lipophilic
(at pH 72) than epinephrine
Phenylephrine hydrochloride prodrug of phenylephrine raised the amount
of phenylephrine in the aqueous humor by 6-8 times and improved
mydriatic activity four fold
Poor aqueous stability
Post aqueous solubility
Eye irritation
Polymereric mucoadhesive vehicle retained in the eye due to non-
covalent bonding with conjuctival mucine
Mucine is capable of picking of 40-80 times of weight of water
Thus prolongs the residence time of drug in the conjuctival sac
Mucoadhesives contain the dosage form which remains adhered to
cornea until the polymer is degraded or mucus replaces itself
Types-
1) Naturally Occurring Mucoadhesives- Lectins Fibronectins
2) Synthetic Mucoadhesives-PVACarbopol carboxy methyl
cellulose cross-linked polyacrylic acid
Drugs incarporated in to this are pilocarpine lidocaine
benzocaine and prednisolone acetate
Mucoadhesives
Objectives
To reduce the frequency of administration
To provide controlled continuous drug delivery
To prolong the pre ocular retention
To avoid or minimize the initial drug concentration peak in the
aqueous humor
To avoid periods of under-dosing that may occur between eye
drop instillation
Novel ocular drug delivery system
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Ocular pharmacokinetics
Ocular structure with routes of drug kinetics
Systemic administration
Limited penetration potential systemic
toxicity
Intraocular implants
Increased risk of retinal detachment and
intravitrealhemorrahge
Intravitreal injections
Increased risk of retinal detachment hemorrhage
and catracts
Topical application
Limited penetration (5) rapid tear
washout poor patient compliance
Flow of lacrimal fluid removes instilledcompounds from the surface of eye
Excess volume is flown to thenasolacrimal duct rapidly
Corneal barrier is formed uponmaturation of epithelial cells
Most apical corneal epithelial cells fromtight junctions that limit the paracellulardrug permeation
These barriers have two parts
Blood retina barrier
Blood-aqueous barrier
Volume
Lacrimation
Tear dilution
Blinking
BARRIERS
Drug loss from ocular surface Lacrimal fluid eye barrier
Blood ocular barriers Others
CORNEL AREA
Drug interaction
Drug protein interaction
Instilled dose
Corneal absorption
Normal tear turn overInduced lacrimation
Conjunctival absorption
Consists of a secretory distributive and collection part
Secretory portion composed of the lacrimalgland Tears are spread over the ocular surfaceby the eyelids during blinking
Collecting system consists of the canaliculithe lacrimal sac the nasolacrimal duct whichhas opening in the inferior
The basal tear flow is of about 12 microlmin(range 05ndash22 microlmin) Reflex stimulationmay increase lacrimation a hundred-fold times
Nasolacrimal drainage
Attainment of optimaldrug concentration
Enhance the poor bioavailability of drugs
To increase bioavailability and duration of ocular
drugs
Use of DDS which provide the controlled and continuous delivery
Maximizing corneal drug absorption and minimizing precorneal drug loss
1Viscosity enhancers
Solution Viscosity Solution Drainage
Enhances viscosity of the formulation
Slows elimination rate from the precorneal area and enhance contact time
Generally hydrophilic polymers- e Methyl cellulose polyvinyl alcohols
polyacrylic acids sodium carboxy methyl cellulose etc
A minimum viscosity of 20 cSt is needed for optimum corneal absorption
Approaches to overcome constraints of
conventional dosage form
2 Prodrugs
Prodrugs enhance corneal drug permeability through modification of the
hydrophilic or lipophilicity of the drug
The method includes modification of chemical structure of the drug molecule
thus making it selective site specific and a safe ocular drug delivery system
Drugs with increased penetrability through prodrug formulations are
epinehrine phenylephrine timolol pilocarpine
Dipivefrine prodrug of epinephrine has 17 times better ability to penetrate
across the cornea Thus is because dipivefrine is 600times more lipophilic
(at pH 72) than epinephrine
Phenylephrine hydrochloride prodrug of phenylephrine raised the amount
of phenylephrine in the aqueous humor by 6-8 times and improved
mydriatic activity four fold
Poor aqueous stability
Post aqueous solubility
Eye irritation
Polymereric mucoadhesive vehicle retained in the eye due to non-
covalent bonding with conjuctival mucine
Mucine is capable of picking of 40-80 times of weight of water
Thus prolongs the residence time of drug in the conjuctival sac
Mucoadhesives contain the dosage form which remains adhered to
cornea until the polymer is degraded or mucus replaces itself
Types-
1) Naturally Occurring Mucoadhesives- Lectins Fibronectins
2) Synthetic Mucoadhesives-PVACarbopol carboxy methyl
cellulose cross-linked polyacrylic acid
Drugs incarporated in to this are pilocarpine lidocaine
benzocaine and prednisolone acetate
Mucoadhesives
Objectives
To reduce the frequency of administration
To provide controlled continuous drug delivery
To prolong the pre ocular retention
To avoid or minimize the initial drug concentration peak in the
aqueous humor
To avoid periods of under-dosing that may occur between eye
drop instillation
Novel ocular drug delivery system
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Systemic administration
Limited penetration potential systemic
toxicity
Intraocular implants
Increased risk of retinal detachment and
intravitrealhemorrahge
Intravitreal injections
Increased risk of retinal detachment hemorrhage
and catracts
Topical application
Limited penetration (5) rapid tear
washout poor patient compliance
Flow of lacrimal fluid removes instilledcompounds from the surface of eye
Excess volume is flown to thenasolacrimal duct rapidly
Corneal barrier is formed uponmaturation of epithelial cells
Most apical corneal epithelial cells fromtight junctions that limit the paracellulardrug permeation
These barriers have two parts
Blood retina barrier
Blood-aqueous barrier
Volume
Lacrimation
Tear dilution
Blinking
BARRIERS
Drug loss from ocular surface Lacrimal fluid eye barrier
Blood ocular barriers Others
CORNEL AREA
Drug interaction
Drug protein interaction
Instilled dose
Corneal absorption
Normal tear turn overInduced lacrimation
Conjunctival absorption
Consists of a secretory distributive and collection part
Secretory portion composed of the lacrimalgland Tears are spread over the ocular surfaceby the eyelids during blinking
Collecting system consists of the canaliculithe lacrimal sac the nasolacrimal duct whichhas opening in the inferior
The basal tear flow is of about 12 microlmin(range 05ndash22 microlmin) Reflex stimulationmay increase lacrimation a hundred-fold times
Nasolacrimal drainage
Attainment of optimaldrug concentration
Enhance the poor bioavailability of drugs
To increase bioavailability and duration of ocular
drugs
Use of DDS which provide the controlled and continuous delivery
Maximizing corneal drug absorption and minimizing precorneal drug loss
1Viscosity enhancers
Solution Viscosity Solution Drainage
Enhances viscosity of the formulation
Slows elimination rate from the precorneal area and enhance contact time
Generally hydrophilic polymers- e Methyl cellulose polyvinyl alcohols
polyacrylic acids sodium carboxy methyl cellulose etc
A minimum viscosity of 20 cSt is needed for optimum corneal absorption
Approaches to overcome constraints of
conventional dosage form
2 Prodrugs
Prodrugs enhance corneal drug permeability through modification of the
hydrophilic or lipophilicity of the drug
The method includes modification of chemical structure of the drug molecule
thus making it selective site specific and a safe ocular drug delivery system
Drugs with increased penetrability through prodrug formulations are
epinehrine phenylephrine timolol pilocarpine
Dipivefrine prodrug of epinephrine has 17 times better ability to penetrate
across the cornea Thus is because dipivefrine is 600times more lipophilic
(at pH 72) than epinephrine
Phenylephrine hydrochloride prodrug of phenylephrine raised the amount
of phenylephrine in the aqueous humor by 6-8 times and improved
mydriatic activity four fold
Poor aqueous stability
Post aqueous solubility
Eye irritation
Polymereric mucoadhesive vehicle retained in the eye due to non-
covalent bonding with conjuctival mucine
Mucine is capable of picking of 40-80 times of weight of water
Thus prolongs the residence time of drug in the conjuctival sac
Mucoadhesives contain the dosage form which remains adhered to
cornea until the polymer is degraded or mucus replaces itself
Types-
1) Naturally Occurring Mucoadhesives- Lectins Fibronectins
2) Synthetic Mucoadhesives-PVACarbopol carboxy methyl
cellulose cross-linked polyacrylic acid
Drugs incarporated in to this are pilocarpine lidocaine
benzocaine and prednisolone acetate
Mucoadhesives
Objectives
To reduce the frequency of administration
To provide controlled continuous drug delivery
To prolong the pre ocular retention
To avoid or minimize the initial drug concentration peak in the
aqueous humor
To avoid periods of under-dosing that may occur between eye
drop instillation
Novel ocular drug delivery system
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Flow of lacrimal fluid removes instilledcompounds from the surface of eye
Excess volume is flown to thenasolacrimal duct rapidly
Corneal barrier is formed uponmaturation of epithelial cells
Most apical corneal epithelial cells fromtight junctions that limit the paracellulardrug permeation
These barriers have two parts
Blood retina barrier
Blood-aqueous barrier
Volume
Lacrimation
Tear dilution
Blinking
BARRIERS
Drug loss from ocular surface Lacrimal fluid eye barrier
Blood ocular barriers Others
CORNEL AREA
Drug interaction
Drug protein interaction
Instilled dose
Corneal absorption
Normal tear turn overInduced lacrimation
Conjunctival absorption
Consists of a secretory distributive and collection part
Secretory portion composed of the lacrimalgland Tears are spread over the ocular surfaceby the eyelids during blinking
Collecting system consists of the canaliculithe lacrimal sac the nasolacrimal duct whichhas opening in the inferior
The basal tear flow is of about 12 microlmin(range 05ndash22 microlmin) Reflex stimulationmay increase lacrimation a hundred-fold times
Nasolacrimal drainage
Attainment of optimaldrug concentration
Enhance the poor bioavailability of drugs
To increase bioavailability and duration of ocular
drugs
Use of DDS which provide the controlled and continuous delivery
Maximizing corneal drug absorption and minimizing precorneal drug loss
1Viscosity enhancers
Solution Viscosity Solution Drainage
Enhances viscosity of the formulation
Slows elimination rate from the precorneal area and enhance contact time
Generally hydrophilic polymers- e Methyl cellulose polyvinyl alcohols
polyacrylic acids sodium carboxy methyl cellulose etc
A minimum viscosity of 20 cSt is needed for optimum corneal absorption
Approaches to overcome constraints of
conventional dosage form
2 Prodrugs
Prodrugs enhance corneal drug permeability through modification of the
hydrophilic or lipophilicity of the drug
The method includes modification of chemical structure of the drug molecule
thus making it selective site specific and a safe ocular drug delivery system
Drugs with increased penetrability through prodrug formulations are
epinehrine phenylephrine timolol pilocarpine
Dipivefrine prodrug of epinephrine has 17 times better ability to penetrate
across the cornea Thus is because dipivefrine is 600times more lipophilic
(at pH 72) than epinephrine
Phenylephrine hydrochloride prodrug of phenylephrine raised the amount
of phenylephrine in the aqueous humor by 6-8 times and improved
mydriatic activity four fold
Poor aqueous stability
Post aqueous solubility
Eye irritation
Polymereric mucoadhesive vehicle retained in the eye due to non-
covalent bonding with conjuctival mucine
Mucine is capable of picking of 40-80 times of weight of water
Thus prolongs the residence time of drug in the conjuctival sac
Mucoadhesives contain the dosage form which remains adhered to
cornea until the polymer is degraded or mucus replaces itself
Types-
1) Naturally Occurring Mucoadhesives- Lectins Fibronectins
2) Synthetic Mucoadhesives-PVACarbopol carboxy methyl
cellulose cross-linked polyacrylic acid
Drugs incarporated in to this are pilocarpine lidocaine
benzocaine and prednisolone acetate
Mucoadhesives
Objectives
To reduce the frequency of administration
To provide controlled continuous drug delivery
To prolong the pre ocular retention
To avoid or minimize the initial drug concentration peak in the
aqueous humor
To avoid periods of under-dosing that may occur between eye
drop instillation
Novel ocular drug delivery system
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
CORNEL AREA
Drug interaction
Drug protein interaction
Instilled dose
Corneal absorption
Normal tear turn overInduced lacrimation
Conjunctival absorption
Consists of a secretory distributive and collection part
Secretory portion composed of the lacrimalgland Tears are spread over the ocular surfaceby the eyelids during blinking
Collecting system consists of the canaliculithe lacrimal sac the nasolacrimal duct whichhas opening in the inferior
The basal tear flow is of about 12 microlmin(range 05ndash22 microlmin) Reflex stimulationmay increase lacrimation a hundred-fold times
Nasolacrimal drainage
Attainment of optimaldrug concentration
Enhance the poor bioavailability of drugs
To increase bioavailability and duration of ocular
drugs
Use of DDS which provide the controlled and continuous delivery
Maximizing corneal drug absorption and minimizing precorneal drug loss
1Viscosity enhancers
Solution Viscosity Solution Drainage
Enhances viscosity of the formulation
Slows elimination rate from the precorneal area and enhance contact time
Generally hydrophilic polymers- e Methyl cellulose polyvinyl alcohols
polyacrylic acids sodium carboxy methyl cellulose etc
A minimum viscosity of 20 cSt is needed for optimum corneal absorption
Approaches to overcome constraints of
conventional dosage form
2 Prodrugs
Prodrugs enhance corneal drug permeability through modification of the
hydrophilic or lipophilicity of the drug
The method includes modification of chemical structure of the drug molecule
thus making it selective site specific and a safe ocular drug delivery system
Drugs with increased penetrability through prodrug formulations are
epinehrine phenylephrine timolol pilocarpine
Dipivefrine prodrug of epinephrine has 17 times better ability to penetrate
across the cornea Thus is because dipivefrine is 600times more lipophilic
(at pH 72) than epinephrine
Phenylephrine hydrochloride prodrug of phenylephrine raised the amount
of phenylephrine in the aqueous humor by 6-8 times and improved
mydriatic activity four fold
Poor aqueous stability
Post aqueous solubility
Eye irritation
Polymereric mucoadhesive vehicle retained in the eye due to non-
covalent bonding with conjuctival mucine
Mucine is capable of picking of 40-80 times of weight of water
Thus prolongs the residence time of drug in the conjuctival sac
Mucoadhesives contain the dosage form which remains adhered to
cornea until the polymer is degraded or mucus replaces itself
Types-
1) Naturally Occurring Mucoadhesives- Lectins Fibronectins
2) Synthetic Mucoadhesives-PVACarbopol carboxy methyl
cellulose cross-linked polyacrylic acid
Drugs incarporated in to this are pilocarpine lidocaine
benzocaine and prednisolone acetate
Mucoadhesives
Objectives
To reduce the frequency of administration
To provide controlled continuous drug delivery
To prolong the pre ocular retention
To avoid or minimize the initial drug concentration peak in the
aqueous humor
To avoid periods of under-dosing that may occur between eye
drop instillation
Novel ocular drug delivery system
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Consists of a secretory distributive and collection part
Secretory portion composed of the lacrimalgland Tears are spread over the ocular surfaceby the eyelids during blinking
Collecting system consists of the canaliculithe lacrimal sac the nasolacrimal duct whichhas opening in the inferior
The basal tear flow is of about 12 microlmin(range 05ndash22 microlmin) Reflex stimulationmay increase lacrimation a hundred-fold times
Nasolacrimal drainage
Attainment of optimaldrug concentration
Enhance the poor bioavailability of drugs
To increase bioavailability and duration of ocular
drugs
Use of DDS which provide the controlled and continuous delivery
Maximizing corneal drug absorption and minimizing precorneal drug loss
1Viscosity enhancers
Solution Viscosity Solution Drainage
Enhances viscosity of the formulation
Slows elimination rate from the precorneal area and enhance contact time
Generally hydrophilic polymers- e Methyl cellulose polyvinyl alcohols
polyacrylic acids sodium carboxy methyl cellulose etc
A minimum viscosity of 20 cSt is needed for optimum corneal absorption
Approaches to overcome constraints of
conventional dosage form
2 Prodrugs
Prodrugs enhance corneal drug permeability through modification of the
hydrophilic or lipophilicity of the drug
The method includes modification of chemical structure of the drug molecule
thus making it selective site specific and a safe ocular drug delivery system
Drugs with increased penetrability through prodrug formulations are
epinehrine phenylephrine timolol pilocarpine
Dipivefrine prodrug of epinephrine has 17 times better ability to penetrate
across the cornea Thus is because dipivefrine is 600times more lipophilic
(at pH 72) than epinephrine
Phenylephrine hydrochloride prodrug of phenylephrine raised the amount
of phenylephrine in the aqueous humor by 6-8 times and improved
mydriatic activity four fold
Poor aqueous stability
Post aqueous solubility
Eye irritation
Polymereric mucoadhesive vehicle retained in the eye due to non-
covalent bonding with conjuctival mucine
Mucine is capable of picking of 40-80 times of weight of water
Thus prolongs the residence time of drug in the conjuctival sac
Mucoadhesives contain the dosage form which remains adhered to
cornea until the polymer is degraded or mucus replaces itself
Types-
1) Naturally Occurring Mucoadhesives- Lectins Fibronectins
2) Synthetic Mucoadhesives-PVACarbopol carboxy methyl
cellulose cross-linked polyacrylic acid
Drugs incarporated in to this are pilocarpine lidocaine
benzocaine and prednisolone acetate
Mucoadhesives
Objectives
To reduce the frequency of administration
To provide controlled continuous drug delivery
To prolong the pre ocular retention
To avoid or minimize the initial drug concentration peak in the
aqueous humor
To avoid periods of under-dosing that may occur between eye
drop instillation
Novel ocular drug delivery system
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Attainment of optimaldrug concentration
Enhance the poor bioavailability of drugs
To increase bioavailability and duration of ocular
drugs
Use of DDS which provide the controlled and continuous delivery
Maximizing corneal drug absorption and minimizing precorneal drug loss
1Viscosity enhancers
Solution Viscosity Solution Drainage
Enhances viscosity of the formulation
Slows elimination rate from the precorneal area and enhance contact time
Generally hydrophilic polymers- e Methyl cellulose polyvinyl alcohols
polyacrylic acids sodium carboxy methyl cellulose etc
A minimum viscosity of 20 cSt is needed for optimum corneal absorption
Approaches to overcome constraints of
conventional dosage form
2 Prodrugs
Prodrugs enhance corneal drug permeability through modification of the
hydrophilic or lipophilicity of the drug
The method includes modification of chemical structure of the drug molecule
thus making it selective site specific and a safe ocular drug delivery system
Drugs with increased penetrability through prodrug formulations are
epinehrine phenylephrine timolol pilocarpine
Dipivefrine prodrug of epinephrine has 17 times better ability to penetrate
across the cornea Thus is because dipivefrine is 600times more lipophilic
(at pH 72) than epinephrine
Phenylephrine hydrochloride prodrug of phenylephrine raised the amount
of phenylephrine in the aqueous humor by 6-8 times and improved
mydriatic activity four fold
Poor aqueous stability
Post aqueous solubility
Eye irritation
Polymereric mucoadhesive vehicle retained in the eye due to non-
covalent bonding with conjuctival mucine
Mucine is capable of picking of 40-80 times of weight of water
Thus prolongs the residence time of drug in the conjuctival sac
Mucoadhesives contain the dosage form which remains adhered to
cornea until the polymer is degraded or mucus replaces itself
Types-
1) Naturally Occurring Mucoadhesives- Lectins Fibronectins
2) Synthetic Mucoadhesives-PVACarbopol carboxy methyl
cellulose cross-linked polyacrylic acid
Drugs incarporated in to this are pilocarpine lidocaine
benzocaine and prednisolone acetate
Mucoadhesives
Objectives
To reduce the frequency of administration
To provide controlled continuous drug delivery
To prolong the pre ocular retention
To avoid or minimize the initial drug concentration peak in the
aqueous humor
To avoid periods of under-dosing that may occur between eye
drop instillation
Novel ocular drug delivery system
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
To increase bioavailability and duration of ocular
drugs
Use of DDS which provide the controlled and continuous delivery
Maximizing corneal drug absorption and minimizing precorneal drug loss
1Viscosity enhancers
Solution Viscosity Solution Drainage
Enhances viscosity of the formulation
Slows elimination rate from the precorneal area and enhance contact time
Generally hydrophilic polymers- e Methyl cellulose polyvinyl alcohols
polyacrylic acids sodium carboxy methyl cellulose etc
A minimum viscosity of 20 cSt is needed for optimum corneal absorption
Approaches to overcome constraints of
conventional dosage form
2 Prodrugs
Prodrugs enhance corneal drug permeability through modification of the
hydrophilic or lipophilicity of the drug
The method includes modification of chemical structure of the drug molecule
thus making it selective site specific and a safe ocular drug delivery system
Drugs with increased penetrability through prodrug formulations are
epinehrine phenylephrine timolol pilocarpine
Dipivefrine prodrug of epinephrine has 17 times better ability to penetrate
across the cornea Thus is because dipivefrine is 600times more lipophilic
(at pH 72) than epinephrine
Phenylephrine hydrochloride prodrug of phenylephrine raised the amount
of phenylephrine in the aqueous humor by 6-8 times and improved
mydriatic activity four fold
Poor aqueous stability
Post aqueous solubility
Eye irritation
Polymereric mucoadhesive vehicle retained in the eye due to non-
covalent bonding with conjuctival mucine
Mucine is capable of picking of 40-80 times of weight of water
Thus prolongs the residence time of drug in the conjuctival sac
Mucoadhesives contain the dosage form which remains adhered to
cornea until the polymer is degraded or mucus replaces itself
Types-
1) Naturally Occurring Mucoadhesives- Lectins Fibronectins
2) Synthetic Mucoadhesives-PVACarbopol carboxy methyl
cellulose cross-linked polyacrylic acid
Drugs incarporated in to this are pilocarpine lidocaine
benzocaine and prednisolone acetate
Mucoadhesives
Objectives
To reduce the frequency of administration
To provide controlled continuous drug delivery
To prolong the pre ocular retention
To avoid or minimize the initial drug concentration peak in the
aqueous humor
To avoid periods of under-dosing that may occur between eye
drop instillation
Novel ocular drug delivery system
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
1Viscosity enhancers
Solution Viscosity Solution Drainage
Enhances viscosity of the formulation
Slows elimination rate from the precorneal area and enhance contact time
Generally hydrophilic polymers- e Methyl cellulose polyvinyl alcohols
polyacrylic acids sodium carboxy methyl cellulose etc
A minimum viscosity of 20 cSt is needed for optimum corneal absorption
Approaches to overcome constraints of
conventional dosage form
2 Prodrugs
Prodrugs enhance corneal drug permeability through modification of the
hydrophilic or lipophilicity of the drug
The method includes modification of chemical structure of the drug molecule
thus making it selective site specific and a safe ocular drug delivery system
Drugs with increased penetrability through prodrug formulations are
epinehrine phenylephrine timolol pilocarpine
Dipivefrine prodrug of epinephrine has 17 times better ability to penetrate
across the cornea Thus is because dipivefrine is 600times more lipophilic
(at pH 72) than epinephrine
Phenylephrine hydrochloride prodrug of phenylephrine raised the amount
of phenylephrine in the aqueous humor by 6-8 times and improved
mydriatic activity four fold
Poor aqueous stability
Post aqueous solubility
Eye irritation
Polymereric mucoadhesive vehicle retained in the eye due to non-
covalent bonding with conjuctival mucine
Mucine is capable of picking of 40-80 times of weight of water
Thus prolongs the residence time of drug in the conjuctival sac
Mucoadhesives contain the dosage form which remains adhered to
cornea until the polymer is degraded or mucus replaces itself
Types-
1) Naturally Occurring Mucoadhesives- Lectins Fibronectins
2) Synthetic Mucoadhesives-PVACarbopol carboxy methyl
cellulose cross-linked polyacrylic acid
Drugs incarporated in to this are pilocarpine lidocaine
benzocaine and prednisolone acetate
Mucoadhesives
Objectives
To reduce the frequency of administration
To provide controlled continuous drug delivery
To prolong the pre ocular retention
To avoid or minimize the initial drug concentration peak in the
aqueous humor
To avoid periods of under-dosing that may occur between eye
drop instillation
Novel ocular drug delivery system
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
2 Prodrugs
Prodrugs enhance corneal drug permeability through modification of the
hydrophilic or lipophilicity of the drug
The method includes modification of chemical structure of the drug molecule
thus making it selective site specific and a safe ocular drug delivery system
Drugs with increased penetrability through prodrug formulations are
epinehrine phenylephrine timolol pilocarpine
Dipivefrine prodrug of epinephrine has 17 times better ability to penetrate
across the cornea Thus is because dipivefrine is 600times more lipophilic
(at pH 72) than epinephrine
Phenylephrine hydrochloride prodrug of phenylephrine raised the amount
of phenylephrine in the aqueous humor by 6-8 times and improved
mydriatic activity four fold
Poor aqueous stability
Post aqueous solubility
Eye irritation
Polymereric mucoadhesive vehicle retained in the eye due to non-
covalent bonding with conjuctival mucine
Mucine is capable of picking of 40-80 times of weight of water
Thus prolongs the residence time of drug in the conjuctival sac
Mucoadhesives contain the dosage form which remains adhered to
cornea until the polymer is degraded or mucus replaces itself
Types-
1) Naturally Occurring Mucoadhesives- Lectins Fibronectins
2) Synthetic Mucoadhesives-PVACarbopol carboxy methyl
cellulose cross-linked polyacrylic acid
Drugs incarporated in to this are pilocarpine lidocaine
benzocaine and prednisolone acetate
Mucoadhesives
Objectives
To reduce the frequency of administration
To provide controlled continuous drug delivery
To prolong the pre ocular retention
To avoid or minimize the initial drug concentration peak in the
aqueous humor
To avoid periods of under-dosing that may occur between eye
drop instillation
Novel ocular drug delivery system
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Dipivefrine prodrug of epinephrine has 17 times better ability to penetrate
across the cornea Thus is because dipivefrine is 600times more lipophilic
(at pH 72) than epinephrine
Phenylephrine hydrochloride prodrug of phenylephrine raised the amount
of phenylephrine in the aqueous humor by 6-8 times and improved
mydriatic activity four fold
Poor aqueous stability
Post aqueous solubility
Eye irritation
Polymereric mucoadhesive vehicle retained in the eye due to non-
covalent bonding with conjuctival mucine
Mucine is capable of picking of 40-80 times of weight of water
Thus prolongs the residence time of drug in the conjuctival sac
Mucoadhesives contain the dosage form which remains adhered to
cornea until the polymer is degraded or mucus replaces itself
Types-
1) Naturally Occurring Mucoadhesives- Lectins Fibronectins
2) Synthetic Mucoadhesives-PVACarbopol carboxy methyl
cellulose cross-linked polyacrylic acid
Drugs incarporated in to this are pilocarpine lidocaine
benzocaine and prednisolone acetate
Mucoadhesives
Objectives
To reduce the frequency of administration
To provide controlled continuous drug delivery
To prolong the pre ocular retention
To avoid or minimize the initial drug concentration peak in the
aqueous humor
To avoid periods of under-dosing that may occur between eye
drop instillation
Novel ocular drug delivery system
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Poor aqueous stability
Post aqueous solubility
Eye irritation
Polymereric mucoadhesive vehicle retained in the eye due to non-
covalent bonding with conjuctival mucine
Mucine is capable of picking of 40-80 times of weight of water
Thus prolongs the residence time of drug in the conjuctival sac
Mucoadhesives contain the dosage form which remains adhered to
cornea until the polymer is degraded or mucus replaces itself
Types-
1) Naturally Occurring Mucoadhesives- Lectins Fibronectins
2) Synthetic Mucoadhesives-PVACarbopol carboxy methyl
cellulose cross-linked polyacrylic acid
Drugs incarporated in to this are pilocarpine lidocaine
benzocaine and prednisolone acetate
Mucoadhesives
Objectives
To reduce the frequency of administration
To provide controlled continuous drug delivery
To prolong the pre ocular retention
To avoid or minimize the initial drug concentration peak in the
aqueous humor
To avoid periods of under-dosing that may occur between eye
drop instillation
Novel ocular drug delivery system
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Polymereric mucoadhesive vehicle retained in the eye due to non-
covalent bonding with conjuctival mucine
Mucine is capable of picking of 40-80 times of weight of water
Thus prolongs the residence time of drug in the conjuctival sac
Mucoadhesives contain the dosage form which remains adhered to
cornea until the polymer is degraded or mucus replaces itself
Types-
1) Naturally Occurring Mucoadhesives- Lectins Fibronectins
2) Synthetic Mucoadhesives-PVACarbopol carboxy methyl
cellulose cross-linked polyacrylic acid
Drugs incarporated in to this are pilocarpine lidocaine
benzocaine and prednisolone acetate
Mucoadhesives
Objectives
To reduce the frequency of administration
To provide controlled continuous drug delivery
To prolong the pre ocular retention
To avoid or minimize the initial drug concentration peak in the
aqueous humor
To avoid periods of under-dosing that may occur between eye
drop instillation
Novel ocular drug delivery system
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Types-
1) Naturally Occurring Mucoadhesives- Lectins Fibronectins
2) Synthetic Mucoadhesives-PVACarbopol carboxy methyl
cellulose cross-linked polyacrylic acid
Drugs incarporated in to this are pilocarpine lidocaine
benzocaine and prednisolone acetate
Mucoadhesives
Objectives
To reduce the frequency of administration
To provide controlled continuous drug delivery
To prolong the pre ocular retention
To avoid or minimize the initial drug concentration peak in the
aqueous humor
To avoid periods of under-dosing that may occur between eye
drop instillation
Novel ocular drug delivery system
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Objectives
To reduce the frequency of administration
To provide controlled continuous drug delivery
To prolong the pre ocular retention
To avoid or minimize the initial drug concentration peak in the
aqueous humor
To avoid periods of under-dosing that may occur between eye
drop instillation
Novel ocular drug delivery system
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Novel ocular drug delivery system
Advantages
Sustained andor controlled drug release
Site-specific targeting
Protect the drug from chemical or enzymatic hydrolysis
Increasing contact time and thus improving bioavailability
Better patient compliance
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Vesicle composed of phospholipid bilayer enclosing
aqueous compartment in alternate fashion
Types 1MLV
2ULV
Polar drugs are incorporated in aqueous compartment while lipophilic drugs
are intercalated into the liposome membrane
Phospholipids used- Phosphotidylcholine Phosphotidic acid Sphingomyline
PhosphotidyleserineCardiolipine
LIPOSOMES
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Behaviour of liposomes as an ocular drug delivery system is due to their
surface charge
Degree of association of liposomes with corneal surface decreased in
order
MLV+ gt SUV+ gt MLV- gt SUV- gtMLV gt SUV
Eg Ocular formulation of Acetazolamide using liposome
Percentage entrapment efficency was 2927 4106 and
4958 for negatively neutral and positively charged
liposomes
Portion of drug released after 9h was 1336338 and 267
for negatively neutral and positively charged liposomes
LIPOSOMES
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
ADVANTAGES DISADVANTAGES
Drugs delivered intact to
various body tissues
Liposomes can be used for both
hydrophilic and hydrophobic
drug
Possibility of targeting and
decrease drug toxicity
The size charge and other
characteristics can be altered
according to drug and desired
tissue
Short shelf life
They need many modification
for drug delivery to special
organs
Cost
Limited drug capacity
Sterilization problems
LIPOSOMES
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Niosomes are non-ionic surfactant based multilamellar(gt005microm)small
unilamellar(0025-005microm) or large unilamellar vesicles(gt01microm)
Structural components used
bull Surfactants (dialkyl polyoxy ethylene ether non ionic surfactant)
bull Cholesterol
Niosomes
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
No difficulty of insertion
No tissue irritation and damage
Provide patient compliance
Biocompatible and have minimum side effects
Prevent the metabolism of drugs from the enzymes
Prolong and sustained release of drug
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Developed by Alza Corporation
Oval flexible ocular insert
Release Rate 20-40mghr
for 7day
Consist of-
Part Material
Drug Reservoir Pilocarpine
Carrier material Alginic acid
Rate controller Ethylene vinyl acetate
copolymer
Energy Source Conc Of Pilocarpine
Delivery Portal Copolymer membrane
Ocusert
Implantable systems
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
2 Contact lenses
Presoaked Hydrophilic lens
Drug Release within 1st 30 Min
Alternate approach incorporate drug either as solution or suspension of
solid monomer mixture
Release rate is up to 180 hr
3 Diffusional Inserts
Central reservoir of drug enclosed in Semi permeable or micro porous
membrane for diffusion of drug
Diffusion is controlled by lacrimal fluid penetrating through it
It prevents continues decrease in release rate due to barrier
Contact lens
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
4Lacrisert Sterile Rod Shaped device
Composition HPC without preservative
Weight5mg
DimensionDiameter125mm Length35mm
Use-Dry eye treatment Keratitis Sicca
5SODI Soluble Ocular Drug Insert
Small water soluble developed for Cosmonauts who could not use their eye drop in liquid condition
Composition Acryl amide Vinyl Pyrolidone Ethylacrylate
Weight 15-16 mg
Softens in 10-15 sec
In 10-15 min turns in viscous liquid
After 30-60min Becomes Polymeric Solution
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Poor patient compliance
Need of surgery
Difficulty in self insertion
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Visulex system
OcuPhor
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Process in which direct current drives ions into cells or tissues
Positive charge they are driven into the tissues at the anode ifnegative charge at the cathode
Fast painless safe and results in the delivery of a high
concentration of the drug to a specific site
Ocular iontophoresis has gained significant interest recently due
to its non-invasive nature of delivery to both anterior and posterior
segment
Iontophoresis
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
CYCLODEXTRINS
Cyclodextrins (CDs) forming inclusion complexes with many
guest molecules
Aqueous solubility of hydrophobic drugs can be enhanced
without changing their molecular structure
They increase corneal permeation of drugs and increase ocular
bioavailability of poorly water soluble drugs
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Insignificant dissociation of the administered complex
within the residence time in the precorneal fluid to release
the free drug into the tear film and at the corneal surface
Precorneal fluid was found to be too low to cause any
significant dissociation of the administered complex
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Ophthalmic Solution Corresponding
Commercial Product
Concentration of
Active Ingredient
Uses
Adrenergic
Epinephrine bitartrate Epitrate Opthalmic
Solution (Ayerst)
2 Chronic open angle
glaucoma
Naphazoline HCl Naphcon Forte (Alcon) 01 Topical ocular
vasoconstricter
Anesthetic
Proparcaine HCl Ophthaine Opthalmic
Solution (Squibb)
05
Rapid acting local
anestheticTetracaine HCl Anacel Sterile
Opthalmic Solution
(Professional
Pharmacel)
05
Antibacterial
Chloramphenicol Ophthochlor Opthalmic
Solution (Parked avis)
05 Used for superficial
infections of eye due to
susceptible
microorganism
Gentamicin Sulfate Garamycin Opthalmic
Solution (Schering)
03
Marketed formulations
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Anticholinergic
Atropine Sulfate Isopto Atropine
Opthalmic Solution
(Alcon)
0125 to 4
Used to produce
mydriasis and
cycloplegiaHomatropine HBr Isopto Homatropine
Opthalmic Solution
(Alcon)
2 and 5
Anti-inflammatory
Dexamethasone
sodium phosphate
opothalmic solution
Decadron Phosphate
(Merck
SharpampDohme)
01
Combats
inflammation due to
mechanicalchemical
or immunologic
causes
Prednisolone sodium
phosphate
Metreton Opthalmic
(Schering)
055
Cholinergic
Pilocarpine HCl Carbine Opthalmic
(Alcon)
025 to 10 Used as a miotic in
treating glaucoma
Marketed formulations
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Ophthalmic
ointment
Commercial
product
Concentration of
active ingredient
Category
Atropine sulfate Atropine sulphate
ophthalmic
ointment
05 and 10 Parasympatholytic
Dexamethasone
sodium phosphate
Decadron phosphate
ophthalmic
ointment (Merk
Sharp ampDohme)
005 Antiinflammatory
Idoxuridine
Opthalmic ointment
Stoxil Opthalmic
ointment (Smith
kline )
05 Antiviral
Sulfisoxazole
diolamine
Gantrisin Opthalmic
Ointment (Roche)
4 Antibacterial
Marketed formulations
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Drug Product Uses
Timolol maleate Timoptic-XE (MERCK amp
CO Inc)
Non-selective beta-
adrenergic
receptor blocking agent
Azithromycin AzaSite (InSite Vision) Antibacterial
Pilocarpine
hydrochloride
Pilopine HS Alcon
Laboratories
Lidocaine hydrochloride Akten Ocular surface anesthesia
Ganciclovir Virgan Acute herpetic
keratitis
Interleukin-2 (IL-2) Cytoryn Activates the
systemic antitumor immunity
Marketed formulations of In-situ drug delivery
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
1Optrex Actimist Eye Spray (Optima-Pharma Germany)
Ingrediants- Soy Lecithin Sodium Chloride Ethanol Phenoxyethanol
Pro-Vitamin B5 (Dexpanthenol) Vitamin A Palmitate Vitamin E Purified
Water
Use- Repair and restore dry irritated eyes
Working
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
2Dry eyes mist (Boots pharmaceuticals)
Use Soothes and relieves dry eyes
Moisturises eyes and lids
Ingrediants
Liposomate isoflavonoids Sodium hyaluronate Camomile extract N
hydroxymethylglycinate Isotonic buffer solution
Marketed Products of liposomes
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied
Although eye drops represent 90 of all opthalmic dosage forms there is
significant effort directed towards new drug delivery systems
Most formulation efforts aim at maximizing ocular drug absorption
through prolongation of the drug residence time
Newer concepts of introducing vesicular prodrugs in situ gel inserts
iontophoresis viscosity and permeation enhancers have been explored
Among the novel delivery vesicular and in situ systems emerged to be
most exploited sections in ocular drug delivery
However for future prespective in depth knowledge about the
physicochemical characteristics of the drug molecule and expected
interaction and implication of entrapping has to be studied