MULTIPLE EMULSUION , STABILITY STUDIES AND APPLICATIONS MICROEMULSION TYPES AND CHARACTERISATION AND APPLICATIONS

1. Guided By :
Dr. HARISH DUREJA
MDU ROHTAK
Presented By :
AMIT ATTRI
M. PHARMA(IP)
Sem.-1st

2. CONTENTS
• Introduction
• Microemulsion
Types of Microemulsion
Preparation of Microemulsion
Characterization of Microemulsion
Advantages of Microemulsion
Stability studies
Uses
Applications of Microemulsion

3. • Multiple Emulsion
Definition
O/W/O Emulsion
W/O/W Emulsion
Methods of preparation
Evaluation of multiple emulsion
Stability studies
Methods to stablize
Applications
• CONCLUSION
• REFERENCE

4. INTRODUCTION
 An emulsion is a thermodynamically unstable system
consisting of atleast two immisible liquid phases one of which
is dispersed as a globules in the other liquid phase stabilised
by a third substance called emulsifying agent.
 An emulsion is a mixture of two or more
immiscible(unblendable) liquids
 In an emulsion one liquid(the dispersed phase) is dispersed in
the other (the continuos phase)

5. MICRO EMULSIONS
“ A micro emulsion is a system, of water ,oil and an
amphiphile which is a single optically isotropic and
thermodynamically stable liquid solution.”
In some aspects, micro emulsions can be considered as
small scale versions of emulsions ,i.e , droplet type
dispersions either of oil-in-water (o/w) or of water in oil
(w/o) with a size range in the order of 5-50nm in drop
radius.

6. TYPES OF MICROEMULSIONS
Three types of micro emulsions are most likely to be formed
depending on the composition:
•Oil in water micro emulsions wherein oil droplets are dispersed
in the continuos aqueous phase
•Water in oil micro emulsions wherein water droplets are
dispersed in the continuous oil phase
•Bi-continuous micro emulsions where in micro domains of oil
and water are inter dispersed within the system.

7. A micro emulsion is considered to be a thermodynamically or
kinetically stable liquid dispersion of an oil phase and a water
phase, in combination with a surfactant.
The key difference between emulsions and micro emulsions are
that the former, whilst they may exhibit excellent kinetic
stability, are fundamentally thermodynamically unstable and
will eventually phase separate
Another important difference concerns their appearance;
emulsions are cloudy while micro emulsions are clear or
translucent

8. PREPARATION OF MICROEMULSION:
Microemulsions were prepared at 27°C by a titration method.
The drug is be dissolved in the lipophilic part of the microemulsion i.e.
Oil and the water phases can be combined with surfactant and a
cosurfactant is then added at slow rate with gradual stirring until the
system is transparent.
The amount of surfactant and cosurfactant to be added and the
percent of oil phase that can be incorporated shall be determined
with the help of pseudo-ternary phase diagram.
Ultrasonicator can finally be used so to achieve the desired size range
for dispersed globules. It is then be allowed to equilibrate

9. Oil-in-water microemulsions were prepared by the titration method.
A mixture of fatty acid and oil was added to a caustic solution to
produce a microemulsion, which was then titrated with a
cosurfactant, an alcohol, until the system turned clear.
It was found that as the chain length of the surfactant increased,
microemulsions with significant transmittances by visible spectrum
could be formed with oils of longer chain lengths.
It was also found that different alcohols affected the formation of
microemulsions in different ways.
The best results, in terms of the greatest percent transmittance
coupled with the widest range of oil (dispersed in water)
concentration, were obtained from short or branched alcohols.

10. Though it has been know that several factors determine whether a w/o
or o/w system will be formed but in general it could be summarised that
the most likely microemulsion would be that in which the phase with
the smaller volume fraction forms the droplets i.e. internal phase.
The surfactants used to stabilise such systems may be:
(i) Non-ionic
(ii) Zwitterionic
(iii) Cationic
(iv) Anionic surfactants

11. Characterization Of Microemulsion :
The droplet size, viscosity, density, turbidity, refractive index, phase
separation and pH measurements shall be performed to characterize
the microemulsion.
The droplet size distribution of microemulsion vesicles can be
determined by either light scattering technique or electron microscopy.
This technique has been advocated as the best method for predicting
microemulsion stability.

12. Advantages Of Microemulsion Over Other Dosage Forms :
 Increase the rate of absorption
 Eliminates variability in absorption
 Helps solublize lipophilic drug
 Provides a aqueous dosage form for water insoluble drugs
 Increases bioavailability
 Rapid and efficient penetration of the drug moiety
 Helpful in taste masking
 Liquid dosage form increases patient compliance.
 Less amount of energy requirement.

13. Stability Studies :
The physical stability of the microemulsion must be determined under
different storage conditions (4, 25 and 40 °C) during 12 months.
Fresh preparations as well as those that have been kept under various
stress conditions for extended period of time is subjected to droplet size
distribution analysis.
Effect of surfactant and their concentration on size of droplet is also be
studied

14. Uses
Microemulsions have many commercially important uses:
Water-in-oil microemulsions for some dry cleaning processes
Floor polishers and cleaners.
Personal care products
Pesticide formulations
Cutting oils.
Pharmaceutical applications of microemulsions Increase bioavailability of
drugs poorly soluble in water.
Topical drug delivery systems

15. Applications of microemulsions
Microemulsions in enhanced oil recovery
Microemulsions as fuels
Microemulsions as coatings and textile finishing
Microemulsions as lubricants, cutting oils and corrosion inhibitors
Microemulsions in detergency
Microemulsions in cosmetics
Microemulsions in agrochemicals
Microemulsion in pharmaceuticals

17. DEFINITION
Multiple emulsions are the emulsion system in which the dispersed phase
contain smaller droplets that have the same composition as the external
phase.
This is made possible by double emulsification hence the systems are
also called as “double emulsion”.
Like simple emulsions, the multiple emulsions are also considered to be
of two types:
•Oil-in-Water-in-Oil (O/W/O) emulsion system
•Water-in-Oil-in-Water (W/O/W) emulsion system

18. O/W/O EMULSION
In O/W/O systems an aqueous phase (hydrophilic) separates internal
and external oil phase.
In other words, O/W/O is a system in which water droplets may be
surrounded in oil phase, which in true encloses one or more oil droplets.

19. W/O/W EMULSION
In W/O/W systems, an organic phase (hydrophobic) separates internal
and external aqueous phases.
In other words, W/O/W is a system in which oil droplets may be
surrounded by an aqueous phase, which in turn encloses one or several
waterdroplets

20.  These systems are the most studied among the multiple emulsions.
 The immiscible oil phase, which separates two miscible aqueous
phases is known as “liquid membrane” and acts as a different barrier
and semi-permeable membrane for the drugs or moieties entrapped
in the internal aqueous phase.

22. Methods of Preparation
Multiple emulsions are best prepared by re- emulsification of primary
emulsion.
The following are the method of multiple emulsions:
 Two Steps Emulsification (Double Emulsification)
 Phase Inversion Technique (One Step Technique)

23. Two Steps Emulsification
(Double emulsification)
Two steps emulsification methods involve re-emulsification of
primary W/O or O/W emulsion using a suitable emulsifier agent.
The first step involves, obtaining an ordinary W/O or O/W primary
emulsion wherein an appropriate emulsifier system is utilized.
In the second step, the freshly prepared W/O or O/W primary
emulsion is re-emulsified with an excess of aqueous phase or oil
phase.
The finally prepared emulsion could be W/O /W or O/W/O
respectively.

26. Phase Inversion Technique
(One Step Technique)
An increase in volume concentration of dispersed phase may
cause an increase in the phase volume ratio, which subsequently
leads the formation of multiple emulsions.
The method typically involves the addition of an aqueous phase
contains the hydrophilic emulsifier
[ Tween 80/sodiumdodecylsulphate (SDS) or Cetyl trimethyl
ammonium salt CTAB)] to an oil phase consisted of liquid
paraffin and containg lipophilic emulsifier (Span80).

28. POSSIBLE MECHANISMS OF DRUG RELEASE FROM
MULTIPLE EMULSIONS
 Diffusion mechanism.
 Micellar transport.
 Thinning of oil membrane.
 Rupture of oil phase.
 Faciliated diffusion (carrier mediated transport).
 Photo -osmotic transport.
 Solubilization of internal phase in the oil membrane.

29. EVALUATION OF MULTIPLE EMULSIONS
Evaluation can be done by :
 Characterization
 Average globule size and size distribution
 No.of globules
 Percentage drug entrapment
 Rheological evaluation
 Zeta potential
 In-vitro stability studies
 In-vitro drug release

30. Stability of Multiple Emulsions
 Emulsion stability is a phenomenon, which depends upon the
equilibrium between water, oil and surfactant.
 Unfortunately multiple emulsions are thermodynamically unstable.
 The possible indications of instability includes:
Leakage of the contents from the inner aqueous phase.
Expulsion of internal droplets in external phase.
Constriction or distension of the internal droplets due to osmotic
gradient across the oil membrane.
Flocculation of internal aqueous phase and multiple emulsion
droplets.
Disruption of oil layer on the surface of internal droplets.
Phase separation.

31. Methods to Stabilize Multiple Emulsions
The followings are some of the attempt or studies made to restore
or strengthen the stability of multiple emulsions :
 Liquid crystal stabilized multiple emulsion.
 Stabilization in presence of electrolytes.
 Stabilization by forming polymeric gel.
 Stabilization by interfacial complexation between non- ionic
surfactant and macromolecules.
 Steric stabilization
 Phase-inversion stabilization of W/O/W emulsion

32. APPLICATIONS
 Applications in Therapeutics & Cosmetics:
Multiple emulsion systems are finding unlimited uses because of their vesicular
structure with innermost phase closely similar to that of liposomal vesicles and the
selective permeability characteristic of liquid membrane.
 In cancer therapy.
 In herbal drugs.
 In taste masking.
 In food industry.
 In drug over dosage treatment.
 In inverse targeting

33. CONCLUSION
 Micro emulsion properties are extremely varied. The extreme
diversity of their practical applications is one consequence.
 One of their disadvantages is the large amount of surfactant
required to stabilize them because of the small dispersion size.
 Although micro emulsion properties are beginning to be
satisfactorily understood, especially the droplet structure, large
research domains remain to be clarified.
 With evaluation of newer techniques of preparation, stabilization,
rheological properties can serves as potential carrier for drugs
,cosmetics ,pharmaceutical agents

34.  Multiple emulsions are complex polydispersed systems where both
oil in water and water in oil emulsion exists simultaneously which are
stabilized by lipophillic and hydrophilic surfactants respectively.
 The ratio of these surfactants is important in achieving stable multiple
emulsions. Among water-in-oil-in-water (w/o/w) and oil-in-water-in-
oil (o/w/o) type multiple emulsions; the former has wider areas of
applications.

35. REFERENCE
 S.P. Vyas , R.K. Khar. Targeted & Controlled drug delivery: novel carrier
systems , 1st ed. New Delhi: CBS publishers ; 2004,page no 303-303
 Micro emulsions as drug delivery system,A.N Lalwani,T.J shah&N.S
Parmar-309
 Targeted &Controlled Drug delivery vyas/khar-303
 Progress in controlled and novel drug delivery system-nk jain
 Advance in controlled &drug delivery A.j khapae&N.K jain-381
 Remington the science and practice of pharmacy 21st ed. page no-745
 Martin’s physical pharmacy and pharmaceutical sciences 6th ed. Page no-
410
 Journals.

36. THANK YOU