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Internal oil droplet

External oil medium

Intermediate water phase

MULTIPLE EMULSION

Presented by: Chinchole Pravin Sonu

(M.PHARM 2nd SEM)DEPARTMENT OF PHARMACEUTICS & QUALITY ASSURANCE

R. C. Patel Institute of Pharmaceutical Education and Research, shirpur.

Emulsion -

• Heterogeneous biphasic system in which one immiscible liquid is dispersed in another in the form of droplet and stabilized by third component called emulsifying agent.

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Types of emulsions -Mostly are of two types,1. w/o system - Dispersed phase - Water Dispersion medium- Oil2. o/w system – Dispersed phase - Oil Dispersion medium- Water

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Multiple emulsions -Novel development in emulsion technology.Complex type of multiple system.

Also called, Emulsion of emulsion. Double or triple emulsion. 4

Internal oil droplet

External oil medium

Intermediate water phase

Types of multiple emulsions -1. w/o/w system –• Oil droplet surrounded by

aqueous phase.

• In most cases, two aqueous phase are identical therefore a W1/O/W1 emulsion is a two component system. In somecases a W1/O/W2 is a three component system.

2. o/w/o system –

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• Water phase separates internal and external oil phase.

Advantages -1. Protect active drug from degradation.2. High encapsulation efficiency.3. Prolonged or controlled drug release

can be achieved.4. Easy to produce and scale up.5. Economical.

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Disadvantages -1. Low thermodynamic stability.2. It is bulkier system.3. Disagreeable taste in some case.

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Theoretical aspects of multiple emulsion phase diagram -

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Formulation and manufacture of multiple emulsion -

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• 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 process

Phase Inversion Technique (One Step Technique)

Membrane Emulsification Technique

1. Two step emulsion/double emulsification.

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Micro Channel Emulsification Process

• Two type of channel:T – junction channel: -

Cross junction channel : -

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Modified Double Emulsion Technique

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Stable

2. Phase inversion.

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3.Membrane Emulsification Technique

1.Microscopic examination – color ,consistancy ,Homogenicity.2. Macroscopic examination – Average globule size & size distribution coarse multiple emulsion > 3micron fine multiple emulsion 1-3 micron micro multiple emulsion <1 micron

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Characterization

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• 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

3.Zeta potential – smouchowski equation

ζ = 4πηµ X 103

εE where, ζ = zeta potential η = viscosity of dispersion medium. µ = migration velosity. ε = dielectric constant of dispersion medium. E = potential gradient.

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4. Entrapment efficiency – dialysis method

c = 100 (1- n1V*/ (n0-n1)v1)

n0 = initial drug concentration of drug in inner aqueous phase n1 = concentration of drug in dialysate V* = constant

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5. Rheological analysis . e.g. viscosity

6. Drug release rate.

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Phosphate saline buffer pH 7.4

Parameters affecting multiple emulsion preparation -1.Composition – a) nature of oil – controls permeability of liquid membrane. controls release rate of solute. b) physiochemical properties – density, viscosity, globule size affect stability 21

2. shear/ agitation – choice of mode of emulsification is

important. high shear disrupts large percent

of multiple drops and leads instability

requirements – primary emulsification – 800 rpm secondary emulsification – 200 rpm

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3. Surfactant – two types a) hydrophilic b) lipophilic concentration of secondary emulsifier

should 1/5 times less than primary. non ionic surfactant mostly preferred due to, better yield of multiple drops non toxic less interact with other compounds. eg.polysorbate

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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

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Methods to stabilize multiple emulsion:

Liquid crystal stabilized multiple emulsion

Stabilization in the presence of electrolytes

Stabilization by forming polymeric gelSteric stabilization

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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.

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• 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.

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• 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.

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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.

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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.

Applications :- 1.Multiple emulsion in controlled release drug delivary. curcumin extract nanoencapsulated in chitosan and

crosslinked with triployphosphate via multiple emulsion shows 96.28% encapsulation efficacy with controllled release.

2.Multiple emulsion in protein delivaryInsulin delivary –

EPA ,DHA, INSULIN multiple emulsion result shows DHA facilitate intestinal insulin absorption without inducing serious damage.

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3.Others – a) For delivery of blood substitutes. b) For drug stability. c) In microencapsulation. d)Thermo reversible multiple emulsions. e) Food processing.

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Thank you

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