Nanoemulsions In Allopathic Drug

Presented byPriya Gupta

LIST OF CONTENTS

2

IntroductionClassificationAdvantageLimitationMethod of preparationCharacterizationApplicationConclusionReferences

INTRODUCTION Nanoemulsion may be defined as the novel drug

delivery system which is thermodynamically stable, isotropic in nature where two immiscible liquid i.e. a water system & an oil system are mixed together to form a single phase by means of an appropriate surfactant.

In nanoemulsion the oil droplets containing the hydrophobic drug that has to be delivered to a targeted organ and the mean droplet diameter ranging 50-500 nm.

Basic structural view of Nanoemulsion system

Nanoemulsion - Classification

Depending on the composition :

O/W : Oil droplets are dispersed in continuous aqueous phase.

W/O : Water droplets are dispersed in continuous oil phase.

Bi-continuous : Microdomains of oil and water are dispersed within the system .

Advantages of Nanoemulsion

Nanoemulsions increase the rate of drug absorption. The very small droplet size causes a large reduction in the gravity force and the

Brownian motion is sufficient for overcoming gravity .This mean that no creaming or sedimentation occurs on storage.

It helps to solubilize lipophilic drugs. It is thermodynamically stable. Various routes like topical, oral, I.V. etc. can be used to deliver the product. It improves the bioavailability of drugs. It can be formulated in variety of formulation such as foam, liquid, spray &

cream. It may be used as a substitute for liposome. Possibilities of controlled drug release & drug targeting. Rapid and efficient penetration of the drug moiety Provides

protection from hydrolysis and oxidation as drug in oil phase.

Limitations of Nanoemulsion

The formulation of nanoemulsion is an expensive process due to size reduction of droplets is very difficult as it required special kind of instruments & process methods .For example homogenizer arrangement is an expensive process.

Oswald ripening could damage the nanoemulsion.

Changing of pH may cause stability problems.

Difference between Emulsions & Nanoemulsions

Emulsions Nanoemulsions

1. Anisotropic2. Appearance is cloudy3. Thermodynamically

unstable.4. Wet gum method, Dry

gum method are used for preparation.

5. Higher surfactant concentration(20-25%)

6. Creaming, sedimentation & phase inversion stability problems may occur.

1. Isotropic2. Appearance is transparent.3. Thermodynamically stable4. Microfludization,

ultrasound generators etc. technique are used for preparation.

5. Lower surfactant concentration(5-10%)

6. Ostwald ripening may occur

Formulation of Nanoemulsions Oil phase -. Castor oil, coconut oil, corn

oil,cottonseed oil, o fish oil, jojoba oil, lard oil,linseed oil, mineral oil, oliveoil, peanut oil etc.

Water- Purified water. Surfactants- polysorbates, tween, span, castor

oilderivatives, stearlyamine, cetyl alcohol, stearyl alcohol, fatty alcohols etc.

Co-surfactants - Ethanol, propanol, propylene glycol etc. Antioxidants - Ascorbic acid, tocopherol etc. Tonicity modifiers - Dextrose, Nacl etc. pH adjusting agents – NaOH HCL. Preservatives - Methyl paraben, Propyl paraben etc.

Preparation of nanoemulsion

High Energy

•High-pressure homogenization•Microfluidization•Ultrasound Energy

Low Energy •Solvent Displacement Method•Phase Inversion Temperature Technique

High-pressure Homogenization

In a high-pressure homogenizer, the dispersion of two liquids (oily phase and aqueous phase) is achieved by forcing their mixture through a small inlet orifice at very high pressure (500 to 5000 psi), which subjects the product to intense turbulence and hydraulic shear resulting in extremely fine particles of emulsion.

This technique makes use of high-pressure homogenizer/ piston homogenizer to produce nanoemulsion of extremely low particle size (up to 1 nm).

Hydraulic shear, intense turbulence and cavitation, act together to yield nanoemulsion with extremely small droplet size.

The resultant product can be re-subjected to high-pressure homogenization until nanoemulsion with desired droplet size is obtained.

Disadvantage: High energy consumption and increase in temperature of emulsion during processing.

Microfluidization

13

It is patented mixing technology which uses the microfluidizer.

The device uses a high pressure positive displacement pump which forces the product through interaction channel which contains ‘microchannels’.

The product flows through a microchannels on to an impingement area resulting in a very fine particle/droplet size formation.

The aqueous and oily phase are processed in an in line homoginizer to yield a coarse emulsion.

Then it is further proceed to microfluidizer to obtain a nanoemulsion.

The coarse emulsion is passed through the interaction channel repeatedly to yield a desired size nanoemulsion.

This method can be used at laboratory and industrial scale.

Ultrasound emulsification

In this method, a probe emits ultrasonic waves (20 kHz) to disintegrate the macroemulsion by means of cavitation forces. By varying the ultrasonic energy input and time, the nanoemulsion with desired properties can be obtained.

Undesirable for thermolabile drugs and macromolecules (retinoid, protein, enzyme and nucleic acid)

Solvent displacement method Oily phase is dissolved in water-miscible organic

solvents, such as acetone, ethanol and ethyl methyl ketone.

The organic phase is poured into an aqueous phase containing surfactant to yield spontaneous nanoemulsion by rapid diffusion of organic solvent.

The organic solvent is removed from the nanoemulsion by a suitable mean, such as vacuum evaporation.

This method can yield nanoemulsion at room temperature and require simple stirring for the fabrication.

This method is used for parenteral preparation.

Phase Inversion TechniqueIn this method the fine dispersions are produced

as the phase inversion occurs which is caused by varying the composition and keeping the temperature constant or vice versa.

phase inversion is widely used in fabrication of cosmetic products, pharmaceutical products (e.g., vesicles for drug delivery), foodstuff and detergents.

charaterization

Average Globule Size And Size Distribution:- a)TEM & SEM - 3 diamensional image b)Light scattering – photon correlation spectroscopy. Viscosity determination: Brookfield viscometer. Refractive Index: Abbe-type Refractometer Zeta Potential : It is used to determine surface charge . Zetasizer is used for determination of zeta potential. Area Of Interface : It can be determined by following

formula. S = 6/d where, S = Total area of Interface (sq.cm) d = Diameter of Globule (cm)

Interfacial Tension: Spinning-drop apparatus can be used to measure the ultra low interfacial tension

Skin permeation test: Franz diffusion cell

Thermodynamic Studies

Prepare number of formulations

Formulations centrifuged for specific period. select stable

formulation kept under heating and cooling cycle. select stable

formulation subjected to a freeze-thaw cycle test

select stable formulation

Parenteral drug delivery

Lipophillic drug can be given by this route. Generally I.V route is preferred.

The lack of flocculation, sedimentation and creaming, combined with a large surface area and free energy, offer obvious advantages over emulsion of larger particle size.

Their very large interfacial area positively influences the drug transport and their delivery, along with targeting them to specific sites.

Frequency of dosage of injection can be reduced throughout the drug therapy.

Parenteral nanoemulsion formulation of the following drugs have been documented- carbamazepine,diazepam,dexamethasone etc.

Parenteral nanoemulsions

Carbamazepine IV injection (Under trial)

Widely used as an anticonvulsant drug, which is a poorly soluble drug with no parenteral treatment available for patients.

Solubility of drug increases by decreasing the particle size upto nanometer

Treatment available for patients i.e. CBZ nanoemulsion given by IV route.

Intranasal Drug delivery Used as a vehicle system for brain targeted drug

delivery. Nanoemulsions loaded with drugs like

risperidone, rizatriptan etc. are very useful in the treatment of CNS disorders like parkinson’s, migraine, meningitis etc.

Preparation of nanoemulsions containing risperidone for its delivery to the brain via nose has been reported. It is inferred that this emulsion is more effective through the nasal rather than intravenous route.

Ocular drug deliveryNanoemulsions increase the contact time of

the drug in the eye.High ability of drug penetration into the

deeper layers of the ocular structure & aqueous humor.

Reduce the need for frequent administration.Nanoemulsion of Dorzolamide Hcl. shows

high therapeutic efficacy & prolonged effect.

Tumor targeted drug deliveryThe use of nanoemulsion formulation, for controlled drug

delivery and targeting because of their submicron size, they can easily be targeted to the tumor area.

Act as a vehicles for targeted drug delivery of various aqueous insoluble anti cancer drugs, photosensitizers, diagnostic agents for cancer therapy.

Development of magnetic nanoemulsion is an innovative approach for cancer therapy. These can be deliver photosensitizers like Foscan to deep tissue layers across the skin thereby inducing hyperthermia.

Pulmonary drug deliveryTo achieve relatively uniform

distribution of drug dose among the alveoli.

Able to transfect pulmonary epithelial cells.

A novel pressurized aerosol system for the pulmonary delivery of salbutamol.

Oral drug deliveryNanoemulsions was developed to

increase oral bioavailability of hydrophobic drugs.

GIT disturbances can be avoided.High concentration of paclitaxal was

observed in the systemic circulation when it is formulated in nanoemulsion form.

Oral lipid nanoemulsion of primaquine

Primaquine is one of the most widely used antimalarial and is the only available drug till date to combat relapsing form of malaria especially in case of Plasmodium vivax and Plasmodium ovale.

Application of PQ in higher doses is limited by severe tissue toxicity including hematological and GI related side effects which are needed to be minimized.

When incorporated into oral lipid nanoemulsion having particle size in the range of 10–200 nm showed effective antimalarial activity against Plasmodium infection in Swiss albino mice at a 25% lower dose level as compared to conventional oral dose.

Transdermal drug deliveryNano sized emulsions are able to easily

penetrate the pores of the skin and reach the systemic circulation.Thus getting channelized for effective drug delivery.

Able to controlled the locally applied drug redistribution through cuteneous blood & lymph vessle system.

w/o nanoemulsions of caffeine, indomethacin, aceclofenac etc. have been developed for transdermal drug delivery.

3.Nanoemulsions As Mucosal Vaccines (Under Trial)

Nanoemulsions are being used to deliver either recombinant proteins or inactivated organisms to a mucosal surface to produce an immune response. nanoemulsion

causes proteins

applied to the mucosal surface facilitates

uptake by antigen

presenting cells

systemic and mucosal immune

response that involves the

production of specific IgG and IgA antibody as well as cellular

immunity

The first applications, an influenza vaccine and an HIV vaccine, can proceed to clinical trials.

32

Top 10 big pharmaceutical companies rank in terms of number of nano-related patents.

Commercially Available Nanoemulsions

Conclusion Nanoemulsions offers several advantages as well

as applications for novel drug delivery and thus receiving increasing attention as drug carriers for improving the delivery of active pharmaceutical ingredients.

They can applicable for almost all routes of drug delivery and therefore hold the promises for different pharmaceutical field.

This new approach could be developed to overcome the problem associated with the treatment of AIDS, genetical disorders and its own stability problems etc.

35

References Vyas S.,Khar R., 2002, Targeted And Controlled Drug

Delivery System, 1st Edition, CBS Publication, 303-329. Jain N.K, 2001, Controlled And Novel Drug Delivery, 1st

Edition, CBS Publication,381-399. P. Shah, D. Bhalodia and P. Shelat, “Nanoemulsion: A

Pharmaceutical Review,” Systematic Reviews in Pharmacy, Vol. 1, No. 1, 2010, pp. 24-32.

Tenjarla, SN (1999), “Microemulsions: An overview and pharmaceutical applications”,

Sarker DK. Engineering of nanoemulsions fordrug delivery. Curr Drug Deliv 2005; 2: 297-310

R.S.R. Murthy,Vesicular and Particulate Drug Delivery Systems, 1st Edition,Career Publication,105-140.