“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.

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Mr. Sagar Kishor Savale
Department of Pharmaceutics
avengersagar16@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
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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, which
in turn encloses one or more oil droplets.
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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 are
identical therefore a W1/O/W1 emulsion
is a two component system. In some
cases a W1/O/W2 is a three component system.
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5. Preparation aspects
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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 process
Phase Inversion Technique (One Step
Technique)
Membrane Emulsification Technique
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7. Two Step Emulsification: -
(Double Emulsification)
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8. Modified Double Emulsion
Technique
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9. Micro Channel Emulsification
Process
 Two type of channel:
T – junction channel: -
Cross junction channel : -
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11. Phase Inversion Technique : -
(One Step Technique)
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12. Membrane Emulsification
Technique
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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:
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14. In vitro drug release:
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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
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16. Methods to stabilize multiple
emulsion:
 Liquid crystal stabilized multiple emulsion
 Stabilization in the presence of electrolytes
 Stabilization by forming polymeric gel
 Steric stabilization
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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.
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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.
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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.
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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.
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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.
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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).
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