MULTIPLE EMULSIONS

BY-ANKITA KISHORE M.PHARM (second SEMESTER) PHARMACEUTICS LAKSHMI NARAIN COLLEGE OF PHARMACY,BHOPAL

CONTENTS
1.Introduction 2.Multiple emulsions 3.Preparation techniques 4.Characterization 5.Appliocations 6.Conclusion 7.references

1.INTRODUCTIONEmulsion

is a heterogeneous system of one immiscible liquid dispersed in another in the form of droplets. Simple emulsion are classified according to the nature of their continuous or dispersed phase as, 1.Water-in-oil (w/o) emulsion 2.Oil-in-water (o/w) emulsion An emulsifier is present to stabilize the system.

2.MULTIPLE EMULSIONSThese

are also known as DOUBLE EMULSIONS. These are more complex system, as the drops of the dispersed phase contain even smaller dispersed droplets, in most cases identical with the continuous phase, but separated physically from the continuous phase, these are known as EMULSIONS OF EMULSIONS

 Based

on the nature of dispersed medium multiple emulsions are of two types1.o/w/o emulsions 2.w/o/w emulsions 1.O/W/O EMULSIONS In this system water droplets may be surrounded by oil phase which in turn enclose one or more oil droplets. 2.W/O/W EMULSION In this system oil droplets may be surrounded by an aqueous phase, which in turn enclose one or several

W/O/W EMULSION

ADVANTAGES OF MULTIPLE EMULSIONS1.A remarkable degree of biocompatibility. 2.Compelete biodegradability. 3.Hydrophilic as well as hydrophobic drug can be entrapped. 4.Protection from the inactivation by the endogenous factors. 5.Increase in drug dosing intervals.

DISADVANTAGES1.Emulsions have short shelf life. 2.These dosage forms are packed in a plastic or glass containers. so, care should be taken in handling and storage.

3.PREPARATION TECHNIQUES For

the preparation of multiple emulsions two different surfactants of opposite nature is used. One surfactant stabilizes the w/o (lipophilic) emulsion while the other stabilizes the o/w (hydrophilic) emulsion. Emulsifier get adsorbed at the surface of droplets during the emulsion formation & prevent them from drawing close enough

METHODS OF PREPARATION1.Two step emulsification (double emulsification) 2.Modified two step emulsification 3.Phase inversion 4.Membrane emulsification method 5.Micro channel emulsification

1.TWO STEP EMULSIFICATION Most

common method because it is easy & gives high yield with reproducibility. Multiple emulsions are prepared by re-emulsification of a primary emulsion. In this method two stages involvedStage 1- It involves the preparation of the primary emulsion either w/o or o/w type which is then re-emulsified with an excess of aqueous or oil

[Aqueous] + [oil + lipophilic surfactant] [w/o emulsion] Stage 2- Generally two emulsifiers are used in the preparation of multiple emulsions. One is lipophilic and other is hydrophilic surfactant. [w/o emulsion] + [ hydrophilic surfactant] [w/o/w emulsion]

EMULSIFICATION TECHNIQUE This

method is different from the conventional two step technique in 2 points1.Sonication & stirring are used to obtain fine, homogenous and stable w/o emulsion. 2. A continuous phase is poured into a dispersed phase for preparing w/o/w emulsion. This modified method gives high

3.PHASE INVERSION (ONE STEP METHOD)A

well defined volume of oil phase is placed in a vessel of pin mixer. An aqueous solution of emulsifier is then introduced successively to the oil phase at the rate of 5 ml/minute, pin mixer rotate steadily at 88 r.p.m. at room temperature. When volume fraction of the aqueous solution of hydrophilic emulsifier exceeds 0.7,

the continuous oil phase is substituted by aqueous phase containing a no. of the vesicular globules among the simple oil droplets, leading to the phase inversion and formation of w/o/w multiple emulsion. Aqueous phase oil, lipophilic W/O/W containing + surfactant emulsion hydrophilic

EMULSIFICATION TECHNIQUEIn

this ,a micro porous glass membrane with a defined pore size can be used as a emulsifying tool. It is based on the principle of dispersing one immiscible phase into other phase by applying pressure. The particle size of the w/o/w emulsion can be controlled with

The

relation between membrane pore size & particle size of emulsion exhibit good correlation as described by the formula-

y=5.03 x + 0.19
wherex=pore size y=mean particle size

5.MICRO CHANNEL EMULSIFICATION

It

is a novel technique. A two step emulsification process employing micro channel as the second step was used for preparing w/o/w emulsions. The w/o/w emulsion entrapment yield was measured flourimatrically and was found

OF MULTIPLE EMULSION1.Average globule size & size distribution 2.Area of interfaces 3.Number of globules 4.Rheological evaluation 5.Zeta potential 6.Percentage drug entrapment 7.In vitro drug release 8.In vitro stability studies

MACROSCOPIC EXAMINATIONPrimary

observations like color, consistency & homogeneity are frequently used to ensure formation of an emulsion. Type of multiple emulsion can be validated by dilution with the external phase.

SIZE & SIZE DISTRIBUTION The

optical microscopy method using calibrated occular & stage micrometer can be utilized for globule size determination of both multiple emulsion droplets as well as droplets of internal dispersed phase. However this method has two main drawbacks1.Simple small drops passes to form

2. If the internal droplets are very small in size these can not be viewed due to reflection light from the oil droplets surface. Various other techniques are used to characterize the emulsion like coulter counter, freeze fracture electron microscopy and scanning electron microscopy are also used to determine average globule size and size distribution

2.AREA OF INTERFACESThe

average globule diameter determined can be used in the calculation of the total area of interface using the formula-

s = 6/d
Where s = total area of interface d = diameter of globules

3.NUMBER OF GLOBULES Number

of globule per cubic millimeter can be measured using a haemocytometer cell after appropriate dilution of the multiple emulsion. The globules in 5 groups of 16 small squares (total 80 small squares) can be counted and the total no. of globules in per cubic mm. is calculated using the formula-

4.PERCENTAGE DRUG ENTRAPMENT%

drug entrapment of drug in the multiple emulsion is generally determined using dialysis, centrifugation, filtration & conductivity measurement. However recently an internal tracer/marker was used to evaluate the entrapment of an impermeable marker molecule contained in the inner phase of

entrapment can be calculated using the following equation-

c=100/[1-n1v*/(n10-n1)v1] v*=v2 + vd(v1 +v2 + v0 )/vs

Wheren10 =initial concentration of drug in inner aqueous phase n1 =concentration of drug in dilysate v1,v2,v0 =represent the volume of

5.RHEOLOGICAL EVALUATIONThe

rheology of multiple emulsion relates to emulsion stability and clinical performance. The viscosity and interfacial elasticity are two major parameter which relate to product rheology. The viscosity of multiple emulsion can be measured by

6.ZETA POTENTIALZeta

potential measurements are pivotal in the designing of surface modified or ligand anchord multiple emulsion system. Zeta potential can be calculated using Smoluchowskis equation from the mobility & electrophoretic velocity of dispersed globules

Zeta

potential was calculated using the following formula = 4 / E x 103 = zeeta potential (m.v.) =viscosity of dispersion medium(poise) = migration velocity (cm/sec.) = dielectric constant of dispersion medium E= potential gradient (voltage applied/distance between

7.IN VITRO DRUG RELEASEThe

drug released from the aqueous inner phase of a w/o/w emulsion can be estimated using the conventional dialysis method using a cellophane tubing. Typically 5 ml. of (w/o/w) multiple emulsion is placed in the dialysis bag & dialysed against 200 ml. of phosphate

sink condition is maintained while sink contents are stirred continuously using a magnetic stirrer. Aliquots are withdrawn at different time interval & estimated using standard procedure & the data are used to calculate the cumulative drug release profile.

8.IN VITRO STABILITY STUDIESEmulsion

stability is determined by phase separation on storage of w/o/w emulsions. Freshly prepared multiple emulsion allowed to stand for one week at room temperature & the volume of aqueous phase separated (vsep) is measured at suitable time interval & % phase separation is calculated using

Formula-

B%=

100 ( vsep / 20 ) [(v1+v2)/v1 +v2+v0)]

wherev1=volume of internal aqueous phase v2=volume of external aqueous phase v3=volume of middle oil phase

5.APPLICATIONSPharmaceutical

applications-

It includes1.Immobilization of enzymes 2.R.B.C. substitute 3.Transdermal delivery 4.Bioavailability 5.Taste masking 6.Drug targeting 7.Prolonged delivery of drug

Some

important applications of multiple emulsions1.Controlled & sustained drug delivery 2.Drug targeting 3.Vaccine adjuvant 4.As a preparation tool for microencapsulation technology. 5.Drug overdose treatment/detoxification 6.Protection action

6.CONCLUSIONMultiple

emulsions known to be promising delivery system for both pharmaceutical and cosmetic materials. The possibility of encapsulating active substances within liquid membranes may lead to interesting opportunities in both fields. Thus the manufacturing,

7.REFERENCES1.Vyas S.P. , Khar R.K., Targeted & controlled Drug Delivery Novel Carrier System , First edition 2002, CBS PUBLISHERS & DISTRIBUTERS, 303-328 2. www.authorstream .com

Thank you