Sanket Pandya TDDS

8/12/2019 Sanket Pandya TDDS

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TRANSDERMAL DRUG DELIVERY:

FORMULATION & EVALUATION

SUBMITTED BY :

Pandya Sanket M.Roll no. 50/09MS (PHARMACEUTICS)NIPER, Raebareli GUIDED BY :

Mr. Md. Sajid AliLecturerNIPER, Raebareli


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Introduction Potential benefits Factors affecting TD route Mechanism of skin permeation Basic components Different types of transdermal patches

Evaluation (physicochemical, invitro, invivo) Recent advancements Conclusion


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Potential benefits oftransdermal routes

The system avoids the chemically hostile GI environment

No GI distress or other physiological contraindications ofthe oral route

Avoids first-pass effect

Allows effective use of drugs with short biological half-life Allow administration of drugs with narrow therapeutic

windows

Provides controlled plasma levels of very potent drugs

Increased patient compliance Painless

Simple application and removal

Flexibility of terminating drug administration by

simply removing the patch


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Controlled drug delivery

Maintain efficacious plasma drug levels for over 1-7 days

Drug input can be promptly interrupted when toxicity

occurs

Disadvantages

Drug that require high blood levels cannot be administered

Drug or drug formulation may cause skin irritation orsensitization

Adhesive may not adhere well to all types of skin

Expensive


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Factors influencing TD route

Physicochemical properties of penetrant (pKa, molecularsize, stability, binding affinity, solubility, partitioncoefficient)

Integrity and thickness of stratum corneum

Density of sweat glands and folicles

Skin hydration

Metabolism

Vehicle effects Time scale of permeation (steady-state vs. transient

diffusion)

Microenvironment of skin surface


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Basic Components Of TDDS

Polymer matrix / Drug reservoir

Drug

Permeation enhancers

Pressure sensitive adhesive (PSA) Backing laminates

Release liner

Other excipients like plasticizers and solvents


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Polymer matrix / Drug reservoir:

Backbone of TDDS

Control the release of the drug from the device.

Prepared by dispersion of drug in liquid or solid state

synthetic polymer base. Natural Polymers: e.g. cellulose derivatives, zein, gelatin,

shellac, waxes, gums, natural rubber and chitosan etc.

Synthetic Elastomers: e.g. polybutadiene, hydrin rubber,polyisobutylene, silicon rubber, nitrile, acrylonitrile, neoprene,

butylrubber etc.

Synthetic Polymers: e.g. polyvinyl alcohol, polyvinylchloride,polyethylene, polypropylene, polyacrylate, polyamide,polyurea, polyvinylpyrrolidone, polymethylmethacrylate etc


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Drug Properties Potency of the drug


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Penetration Enhancers

Activity of penetration enhancers Interaction with the polar head groups of lipid viahydrogen and ionic bonding

Increase volume of the aqueous layer : swelling andhydration

Alter the packing of the lipid tailsdisorder andtraverse by a lipid-like penetrant

Solvents DMSO, propylene glycol, ethanol

Cosolvent Azone (1-dodecylazacycloheptane-2-one) Cis-unsaturated oleic acid Additive : PGincrease solubilizing ability for lipid-like

materials Flip over to insert between the hydrophobic groups of the

membrane lipids

increasing fluidity of lipid


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Pressure-sensitive adhesive ASTM (American Society for Testing and Materials) definition :

viscoelastic material which remains permanently tacky

Remove from a surface without leaving a residue

Natural or synthetic rubbers, polyacrylates, silicone

Release liner (release paper, peel-away strip)

Sheet that serve as a protectant or carrier for an adhesive film(easily removed)

Paper, polystyrene or polyester films with coating of silicone, long-chain branched polymers, chromium complex, fluorochemicals or

various hard polymers

Rate controlling membranes Ethyl vinyl (EVA) copolymers

Microporous polyethylene or polypropylene


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Backing Laminate: High flexibility

Good oxygen transmission

High moisture vapor transmission rate

EG. vinyl, polyethylene and polyester films

Other excipients: Various solvents such as chloroform, methanol, acetone,

isopropanol and dichloromethane are used to prepare drug

reservoir. In addition plasticizers such as dibutylpthalate,

triethylcitrate, polyethylene glycol and propylene glycol areadded to provide plasticity to the transdermal patch


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Figure 1: Design of matrix type

transdermal patch


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Figure 2: Design of reservoir type

transdermal patch


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Figure 3: Design of micro reservoir

type transdermal patch


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Figure 4: Design of drug in adhesive

type transdermal patch


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Evaluation

Physicochemical evaluation.

Invitro studies

Invivo studies


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Physicochemical evaluation

THICKNESS

TACK PROPERTIES

UNIFORMITYOF WEIGHT

CONTENTUNIFORMITY

FOLDINGENDURANCE

MOISTURECONTENT

TENSILESTRENGTH

WATER VAPOURTRANSMISSION

STUDIES

PEELADHESION

PROPERTIES


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Invitro Release studies

The Paddle over Disc: (USP apparatus 5 )

The Cylinder modified USP Basket: (USPapparatus 6 )

The reciprocating disc: (USP apparatus 7)Diffusion Cells e.g. Franz Diffusion Cell and its

modification Keshary- Chien Cell


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pH of the dissolution medium= 1-5

Temp = 320C ( physiological skin temp. )

100 rpm

Concn

of drug determined


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Invivo studies :Animal models

mouse, hairless rat, hairless dog, hairless rhesus

monkey, rabbit, guinea pig etc

Human volunteerscollection of pharmacokinetic and pharmacodynamic

data following application of the patch to human

volunteers.Phase I,II.III.IV clinical trials

Skin irritation studiesWhite albino rats, mice or white rabbits are used

to study any hypersensitivity reaction on the skin. Stability studies


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RECENT ADVANCES

Rolf Amphoteric enhancers : SLS, lauryl amine oxide, Azone

decylmethylsulfoxide, lauryl ethoxylate, octanol

PSA (pressure sensitive adhesives) Adhesive matrix, multilaminated PSA matrix

Adverse interaction between the drug, exicipents, cosolvents

and permeation enhancers in reservoir and matrix-typesystem

Silicone PSA : tack, adhesion, cohesive strength

Polydimethylsioxane PSA : biocompatibility and high

permeability


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Actiderm (Bristol Myers Squibb) Path with no drug as occlusive dressing

Placed over topically applied corticosterids to enhance

efficacy by promoting hydration of the stratum corneum Laminated reservoir system by

Hercon Steady-state blood levels for extended periods

Two or four layers, including a backing membrane, thedrug reservoir, a rate-controlling membrane, and anadhesive

Ketobemidone and carbonate esterprodrug Prodrug with isopropyl myristate, ethanol and ethanol-

water readily penetrate the skin

Enzymatic conversion, high solubility of prodrug in polarand apolar solvents


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EXAMPLES OF TRANSDERMALAPPLICATIONS

Drug Trade Name Type of

Devices

Indication

Scopolamine Transderm-Scop

Reservoir Motionsickness

Nitroglycerine Transderm-Nitro

Reservoir Angina

Nitro-Dur Monolithic

Nitrodisc Monolithic

Estradiol Estraderm Reservoir andethanolenhancer

Hormonetreatment


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TABLE 2 TRANSDERMAL PRODUCTS UNDER

DEVELOPMENT

Drug Trade name Producer-Marketer

Minocycline Sunstar American Cyanamide,Takeda

Estradiol+Norethisterone

EstracombiTIS

Ciba-Geigy, Alza

DHEA Pharmedic

Fentanyl Duragesic Alza pharmaceuticals

Triamcinolone acetonide

Whitby Pharm.


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Conclusion

Critical parameter in designing a TDS Drug stability, physical stability of the formulation,irritation and sensitization properties, preservation andesthetic acceptability

Vehicle affect drug bioavailability

Maximizing drug penetration into skin

Two mechanism that manipulate thediffusion of a drug across the skin Change the degree of interaction between drug and

vehicle(drugs thermodynamic activity)

Changes in the stratum corneum that will affect itsdiffusional resistance (vehicle-barrier interaction)


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Transdermal therapy

70% or more of all drugs : potentially delive.redby TDS

Limitation : drug potency, skin permeability,topical reaction, cutaneous metabolism, delivery

by small volume of skin Further TTS : use of prodrug, penetration

enhancer and specific nontoxic enzymeinhibitors, Iontophoresis


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Sanket Pandya TDDS