BY, BY,

V. REKHAV. REKHA

M.PHARMACYM.PHARMACY

PHARMACEUTICSPHARMACEUTICS

MULTIPLE EMULSIONS

INTRODUCTIONINTRODUCTIONEmulsions may be described as heterogenous systems,

where one immiscible liquid is dispersed in another in the form of droplets and stabilized by a third component called emulsifying agent

The emulsions can be divided up into:1. Oil in water (O/W) emulsions and2. Water in Oil (W/O) emulsions.

1. O/W Emulsion:By dispersion of oil into water the oil drops are the

inner, dispersed phase. Water is the outer, continuous phase.

2. W/O Emulsion:

By dispersion of water into oil the water drops are the

Inner, dispersed phase. Oil is the outer, continuous phase.

Oil phase

Aq phase

Oil phase

MULTIPLE EMULSIONS:MULTIPLE EMULSIONS:

Multiple emulsion are complex system which

consist of both w/o and o/w at the same time.

There are potential matrices for the encapsulation of

biactive compounds and for the controlled release

compounds w/o/w multiple emulsion are system where small

water droplets are entrapped within larger oil droplets and they are disperse continous water phase

Because of presense of reseroir phase that can be use to prolong release of active ingredients.

This is made possible by double emulsification hence the systems are also called as “Double emulsions”.

These are also called as “Liquid membrane systems” as the liquid film which separates the liquid phases acts as a thin semipermeable film through which solute must diffuse in order to transverse from one phase to another.

Multiple emulsions are thermodynamically unstable.

They are often stabilized by using a combination of hydrophilic & hydrophobic surfactants.

The ratio of these surfactants is important in achieving stable multiple emulsions.

TYPES:TYPES: With optical microscopy method,

multiple emulsions are classified as, 1. coarse (>3 micrometer in diameter) 2. Fine (1-3 micrometer in diameter) 3. Micro-multiple emulsions (<1 micrometer in

diameter)

W/O/W Type of emulsionW/O/W Type of emulsion

O/W/O type of emulsionO/W/O type of emulsion

Multiple emulsions can also be formulated by using either Multiple emulsions can also be formulated by using either oo11/o/o22/o/o11 systems or o systems or o11/o/o22/w formulations are possible. /w formulations are possible.

Examples of both are shown in FigureExamples of both are shown in Figure

Multiple emulsion w/o/w contain two emulsifiers:

1 Low HLB surfactant (Hydrophobic in nature)

2 High HLB surfactant (Hydrophilic in nature)

Low HLB surfactant use in disperse phase High HLB surfactant use in continuous

phase.

EMULSIFYING AGENTSEMULSIFYING AGENTSEmulsifier or surface active agent [SAA] is

molecule which has two parts, one is hydrophilic and the other is hydrophobic. Upon the addition of SAA, it tends to form monolayer film at the oil/ water interface.

surfactants

Anionic Sodium oleate Pottasium oleateGlyceryl monostearate

cationic Benzalkonium chloride

Non ionicspan 80span20Tween 20Tween 60Tween 80

Mechanism of release of drug:Mechanism of release of drug:

1 Primary interface lying between the inner w/o phase contains the low HLB surfactant.

2 Secondary interface lying between droplets and continuous aqueous phase. Low and high HLB surfactant present in it. When hydrophilic surfactant in the continuous aqueous phase exceed its critical micelle concentration the resultant micelles may solubilize the hydrophobic surfactant present in oil phase.

METHOD OF PREPARATIONMETHOD OF PREPARATION

1) Solvent evaporation method

2) Two step emulsification.

3) Phase inversion technique.

SOLVENT EVAPORATION TECHNIQUE

TWO STEP EMULSIFICATION/ DOUBLE EMULSIFICATION

APLLICATONS OF MULTIPLE APLLICATONS OF MULTIPLE EMULSIONSEMULSIONS Multiple emulsions finds wide range of

applications in controlled or sustained drug

delivery, targeted delivery, taste masking,

bioavailability enhancement, enzyme

immobilization, etc.

It will be able to provide a novel carrier system

for drugs, cosmetics and pharmaceutical agents.

1. Hemoglobin multiple emulsion having specified properties is suitable for provision of oxygen as a blood substitute and other oxygen transfer processes.

2. W/O/W multiple emulsions are systems of potential interest in the oral administration of insulin. Although it has been shown that a single oral administration of insulin-loaded W/O/W multiple emulsion to diabetic rats led to the significant decrease of blood glucose.

3. (w/o/w) multiple emulsions and polymeric nanoparticle formulations containing influenza virus surface antigen hemagglutinin (HA) are thought to be suitable carriers for a vaccine delivery system.

4. Using a water-in-oil-in-water multiple emulsion system developed for pulmonary drug targeting, the effectiveness of tetrandrine as an antifibrotic agent.

5. To develop a prolonged and sustained release preparation , an albumin micro-sphere-in-oil-in-water emulsion was prepared. Tegafur was used as a model drug.

6. Vitamin c has been widely used in formulations of skin care products.

7. Multiple emulsions are also used in topical application ex… a w/o/w emulsion of Metronidazole.

REFERENCESREFERENCES1) Pharmaceutical Emulsions and Suspensions, edited by Francoise

Nielloud Gilberte Marti-Mestres.

2) Pharmaceutical Dosage Forms: Disperse systems, vol.3, second edition, Edited by Herbert A.Liberman, Martin M. Rieger and Gilbert S. Banker.

3) some studies on Multiple Emulsions by G.Vishwanadham, (Ph.D thesis, KU)

4) Advances in Controlled and Novel Drug Delivery Systems, Edited by N.K. Jain.

5) Targeted and controlled Drug Delivery Novel Carrier Systems

by -S.P. Vyas and R.K. Khar. http://www.aapsj.org/view.asp http://www.blackwell-synergy.com http://www.rsc.org/delivery/_ArticleLinking http://cat.inist.fr http://iufost.edpsciences.org