NDDS

1. 11
MULTIPLE EMULSIONS
Presented by:
Chinchole Pravin Sonu
(M.PHARM 2nd
SEM)
DEPARTMENT OF PHARMACEUTICS & QUALITY
ASSURANCE
R. C. Patel Institute of Pharmaceutical
Education and Research, shirpur.

2. 22
CONTENT
Introduction
Preparation Aspects
Methods Of Preparation
Characterization
Stability
Drug Release Mechanisms And Models
In Vivo Study Of Multiple Emulsion
Applications
References

3. 33
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 semipermeable
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.
Internal oil droplet
External oil medium
Intermediate water phase

4. 44
 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.

5. 55
Preparation aspects

6. 66
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

7. 77
Two Step Emulsification: - (Double Emulsification)

8. 88
Modified Double Emulsion Technique
Stable
1:4:5

9. 99
Micro Channel Emulsification Process
Two type of channel:
T – junction channel: -
Cross junction channel : -

10. 10

11. 1111
Phase Inversion Technique : - (One Step Technique)

12. 1212
Membrane Emulsification Technique

13. 1313
Characterization
 Average globule size & size distribution:
 Area of interfaces:
 Number of globules:
 Rheological evaluation:
 Zeta potential:
 Calculated using the Zeta-potentiometer.
ζ = 4πηµ X 103
εE
 Percent drug entrapment:

14. 1414
In vitro drug release:
Phosphate saline buffer
pH 7.4

15. 1515
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
 Methods to stabilize multiple emulsion:
 Liquid crystal stabilized multiple emulsion
 Stabilization in the presence of electrolytes
 Stabilization by forming polymeric gel
 Steric stabilization

16. 1616
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.
 (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.

17. 1717
 (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.
 (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.

18. 1818
In-Vivo 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.

19. 1919
Applications
Controlled and Sustained Drug Delivery
Drug Targeting
Vaccine Adjuvant
Cosmetics preparation
Taste masking of the drug

20. 2020
References
 Abraham Aserin., Multiple Emulsions Technology And Applications,
Wiley-interscience, A John Wiley & Sons, 2007, Inc., Publication; 111-324
 Vyas S. P. And Khar R. K., Targeted And Controlled Drug Delivery
System, 1st
Edition , 2002, CBS Publication; 303-329.
 Jain N. K., Controlled And Novel Drug Delivery, 1st
Edition 2001, CBS
Publication; 381-399.
 TORII Lab - Research - Droplet Formation In A Microchannel Network.
 TORII Lab - Research - Multiple Emulsions.
 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).
 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).

21. 2121