1

MULTIPLE EMULSIONS

Mr. Sagar Kishor Savale

Department of Pharmaceuticsavengersagar16@gmail.com

2015-016

Department of Pharmacy (Pharmaceutics) | Sagar savale

2

CONTENTS Introduction Preparation Aspects Methods Of Preparation Characterization Stability Drug Release Mechanisms And Models In Vivo Study Of Multiple Emulsion Applications Conclusion References

3

Introduction “Emulsion of emulsion”, “double or triple emulsion” Dispersed phase contain smaller droplets that have

the same composition as the external phase. Liquid film which separate the liquid phases acts as a

thin semi permeable film through which solute must diffuse in order to travel from one phase to another – “Liquid Membrane System”

Two types: - Oil-in-water-in-oil (O/W/O) emulsion system. Water-in-oil-in-water (W/O/W) emulsion system.

O/W/O is a system in which water droplets may be surrounded in an oil phase, whichin turn encloses one or more oil droplets.

Internal oil droplet

External oil medium

Intermediate water phase

4

W/O/W is a system in which an oil droplet may be surrounded by an aqueous phase,which in turn encloses one or several

water droplets.

In most cases, two aqueous phase areidentical therefore a W1/O/W1 emulsionis a two component system. In somecases a W1/O/W2 is a three component system.

5

Preparation aspects

6

Method of Preparation Either by the re-emulsification of a

primary emulsion or they can be produced when an emulsion inverts from one type to another.Two Step Emulsification (Double

Emulsification)Micro channel emulsification processPhase Inversion Technique (One Step

Technique)Membrane Emulsification Technique

7

Two Step Emulsification: - (Double Emulsification)

8

Modified Double Emulsion Technique

9

Micro Channel Emulsification Process Two type of channel:

T – junction channel: -

Cross junction channel : -

10

11

Phase Inversion Technique : - (One Step Technique)

12

Membrane Emulsification Technique

13

Characterization Average globule size & size distribution: Area of interfaces: Equation:- S=6/d Number of globules: No. of globules x dilution x4000 No. of small squares counted Rheological evaluation: Zeta potential: Calculated using the Zeta-potentiometer.

ζ = 4πηµ X 103

εE

Percent drug entrapment:

14

In vitro drug release:

Phosphate saline buffer pH 7.4

15

Stability Depending upon equilibrium between water, oil and surfactant. Unfortunately multiple emulsion are thermodynamically

unstable. Possible indication of instability include:

Leakage of the contents from the inner aqueous phases Rupture of oil layer on the surface of the internal droplet i. e.

expulsion of internal droplet in external phase. Shrinkage and swelling of the internal drops due to osmotic

gradient across the oil membrane Phase separation Coalescence of the internal

droplets and multiple emulsion drops

16

Methods to stabilize multiple emulsion:

Liquid crystal stabilized multiple emulsion Stabilization in the presence of

electrolytes Stabilization by forming polymeric gel Steric stabilization

17

Drug Release Mechanisms And Models

1) Diffusion mechanism: This is most obvious transport mechanism where

unionized hydrophobic drug diffuses through the oil layer (Semi permeable liquid membrane) in the stable multiple emulsions.

2) Micellar transport: Inverse micelles play key role in this transport

mechanism. Inverse micelles consisting of nonpolar part of surfactant lying outside and polar part inside encapsulate hydrophilic drug in core and permeate through the oil membrane because of the outer lipophilic nature.

Inverse micelle can encapsulate both ionized and unionized drug.

18

3) Thinning of the oil membrane: Transport of water through thin oil membrane region. In

this area, it is easier for the water or drug to permeate because of small oily region. Thinning of the oil membrane takes place primarily due to osmotic pressure difference between two aqueous phases.

4) Rupture of oil phase: According to this mechanism rupturing of oil membrane

can unite both aqueous phases and thus drug could be released easily.

5) Facilitated diffusion (Carrier-mediated transport): This mechanism involves a special molecule (carrier)

for the transfer of hydrophilic, ionic molecule from internal to external aqueous phase. This carrier molecule combines with the drug and makes it compatible to permeate through the oil membrane (lipophilic, nonionic).

This type of mechanism behaves like ‘pumping system’ where the carrier molecule act as pump and transfer drugs from internal to external aqueous phase.

19

6) Release by Breakup after Swelling:The swelling/breakdown process occurs

only if there is a concentration gradient between the internal and the external aqueous phases.

20

In-Vivo release Study Of Multiple Emulsion

Blood, Lymph, Cerebrospinal fluid and Urine are all basically aqueous media and sustained drug delivery to these organs can be claimed if the rate of partitioning from oil into an aqueous media is slow and controllable.

W/O/W emulsion could breakdown rapidly in vivo due to an osmotic effect.

The use of isotonic system and/or the creation of thick interfacial layer or gelled system that can withstand the osmotic stress provides system that may have controlled drug release characteristics in vivo.

21

Applications Controlled and Sustained Drug Delivery

Drug Targeting

Vaccine Adjuvant

Cosmetics preparation

Taste masking of the drug Haemoglobin Multiple emulsion as an oxygen

Delivery system.

22

References 1. Abraham Aserin., Multiple Emulsions Technology And

Applications, Wiley-interscience, A John Wiley & Sons, 2007, Inc., Publication; 111-324

2. Vyas S. P. And Khar R. K., Targeted And Controlled Drug Delivery System, 1st Edition , 2002, CBS Publication; 303-329.

3. Jain N. K., Controlled And Novel Drug Delivery, 1st Edition 2001, CBS Publication; 381-399.

4. TORII Lab - Research - Droplet Formation In A Microchannel Network.

5. TORII Lab - Research - Multiple Emulsions.

6. Jong-wook Ha And Seung-man Yang., Breakup Of A Multiple Emulsion Drop In A Uniform Electric Field., Journal Of Colloid And Interface Science 213, 92–100 (1999).

7. Jim Jiao and Diane J. Burgess., Rheology and Stability of Water-in-Oil-in-Water Multiple Emulsions Containing Span 83 and Tween 80., AAPS PharmSci 2003; 5 (1) Article 7 (http://www.pharmsci.org).

23

Thank you