4. Microemulsion
• Microemulsions are thermodynamically stable dispersions of oil and
water stabilized by a surfactant and, in many cases, also a
cosurfactant.
• Microemulsions can have characteristic properties such as ultralow
interfacial tension, large interfacial area and capacity to solubilize
both aqueous and oil-soluble compounds.
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Theories of Microemulsion Formation
1. Interfacial or mixed film theories.
2. Solubilization theories.
3. Thermodynamic treatments.
5. Interfacial/Mixed Film Theories:
• They considered that the spontaneous formation of microemulsion
droplets was due to the formation of a complex film at the oil-water
interface by the surfactant and co-surfactant.
• This caused a reduction in oil-water interfacial tension to very low values
(from close to zero to negative)
• equation. γi = γo/w -πi
Where,
γ o/w = Oil-water interfacial tension without the film present
πi = Spreading pressure
γi =Interfacial tension
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6. Mechanism of curvature of a duplex film:
• The interfacial film should be curved to form small droplets to explain
both the stability of the system and bending of the interface.
• A flat duplex film would be under stress because of the difference in
tension and spreading of pressure on either side of it.
• Reduction of this tension gradient by equalizing the two surface tensions
is the driving force for the film curvature.
• It is generally easier to expand the oil side of an interface than the water
side and hence W/O microemulsion can be formed easily than O/W
microemulsion.
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7. Solubilization Theories:-
• Illustrated the relationship between reverse micelles and W/O
microemulsion with the help of phase diagrams.
• The inverse micelle region of ternary system i.e. water, pentanol and
sodium dodecyl sulphate (SDS) is composed of water solubilized reverse
micelles of SDS in pentanol.
• Addition of O-xylene up to 50% gives rise to transparent W/O region
containing a maximum of 28% water with 5 % pentanol and 6% surfactant
(i.e. microemulsions).
• These four component systems could be prepared by adding hydrocarbon
directly to the inverse micellar phase by titration.
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8. Thermodynamic theory
• The process of formation of oil droplets from a bulk oil phase is
accompanied by an increase in the interfacial area ∆A, and hence an
interfacial energy ∆G .
• The entropy of dispersion of the droplets is equal to T ∆ S and hence the
free energy of formation of the system is given by the expression.
∆Gf = γ ∆a - T ∆S
Where,
∆Gf = free energy of formation
∆A = change in interfacial area of microemulsion
∆ S = change in entropy of the system
T = temperature
γ = surface tension of oil water interphase
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9. • When the interfacial tension is made sufficiently low that the interfacial
energy becomes comparable to or even lower than the entropy of
dispersion.
• The dominant favorable entropic contribution is very large dispersion
entropy arising from the mixing of one phase in the other in the form of
large number of small droplets.
• The free energy of formation of the system becomes zero or negative.
• This explains the thermodynamic stability of micro emulsions.
• The co-surfactant along with surfactant lower the interfacial tension to a
very small even transient negative value .
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10. Main three components
1. Oil phase
2. Surfactant
3. Cosurfactant
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12. Oil Component
• As compare to long chain alkanes, short chain oil penetrate the tail group
region to a greater extent and resulting in increased negative curvature (and
reduced effective HLB).
• Following are the different oil are mainly used for the formulation of
microemulsion:
1. Saturated fatty acid-lauric acid, myristic acid,capric acid
2. Unsaturated fatty acid-oleic acid, linoleic acid,linolenic acid
3. Fatty acid ester-ethyl or methyl esters of lauric, myristic and oleic acid.
• The main criterion for the selection of oil is that the drug should have high
solubility in it.
• This will minimize the volume of the formulation to deliver the therapeutic
dose of the drug in an encapsulated form.
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13. Surfactants
• It is to lower the interfacial tension which will ultimately facilitates
dispersion process and provide a flexible around the droplets.
• Generally, low HLB (3-6) surfactants are suitable for w/o
microemulsion, whereas high HLB (8-18) are suitable for o/w
microemulsion.
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14. Co surfactants
• They allow the interfacial film sufficient flexible to take up different
curvatures required to form microemulsion over a wide range of
composition.
1. Short to medium chain length alcohols (C3-C8) reduce the
interfacial tension and increase the fluidity of the interface.
2. Surfactant having HLB greater than 20 often require the presence
of cosurfactant to reduce their effective HLB to a value within the
range required for microemulsion formulation.
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15. 7/28/2013 uka tarsadia university 15
• a) by reducing the interfacial tension
• b) By increasing the flexibility and fluidity of the interface by positioning
itself between the surfactant tails which alters the solvent properties of both
the dispersed and continuous microemulsion phases;
• c) by lowering overall viscosity.
• d) by being often soluble in both organic and aqueous phases, co-
surfactants help solubilise poorlysoluble compounds (e.g., peptides, vitames
16. Types of micro emulsion
• O/W Microemulsion
• W/O Microemulsion
• Bi continuous Microemulsion
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17. Phase Behaviour
• For four or more components
pseudo ternary phase diagrams are
used to study the phase behaviour.
• In this diagram a corner represent a
binary mixture of two components
such as water/drug, oil/drug or
surfactant/co-surfactant.
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18. • With high oil concentration surfactant forms reverse micelles capable of
solubilizing water molecules in their hydrophilic interior.
• Continued addition of water in this system may result in the formation
of W/O micro emulsion in which water exists as droplets surrounded
and stabilized by interfacial layer of the surfactant / co-surfactant
mixture.
• Finally, as amount of water increases, this lamellar structure will break
down and water will form a continuous phase containing droplets of oil
stabilized by a surfactant / co-surfactant (O/W microemulsions)
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19. Preparation of Microemulsion
• Following are the different methods are used for the
preparation of microemulsion:
1. Phase titration method
2. Phase inversion method
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20. 7/28/2013 uka tarsadia university 20
• 1)dilution of an oil-surfactant mixture with water.(w/o)
• 2) dilution of a water-surfactant mixture with oil.(o/w)
• 3) mixing all components at once. In some systems, the order of
ingredient addition may determine whether a microemulsion forms or not.
•e.g.(w/o)
soybean oil, ethoxylated mono- and di-glycerides as surfactants and a
mixture of sucrose and ethanol as the aqueous phase.
Transparent microemulsions resulted from dilution of the oil-surfactant
mixtures with water along several regions in the pseudo-ternary phase
diagram.
Phase titration method
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Phase inversion method :
Phase Inversion Temperature (PIT), i.e., the temperature range in which an
o/w microemulsion inverts to a w/o type or vice versa.
• using non-ionic surfactants, polyoxyethylene are very susceptible to
temperature since surfactant solubility (in oil or water) strongly depends on
temperature.
With increasing temperature, the polyoxyethylene group becomes
dehydrated, altering the critical packing parameter which results in phase
inversion.
• For ionic surfactants, increasing temperatures increase the electrostatic
repulsion between the surfactant headgroups thus causing reversal of film
curvature.
Hence the effect of temperature is opposite to the effect seen with non-ionic
surfactants.
22. Parameters
Studied
Techniques Used
Phase Behaviour Phase contrast microscopy and freeze fracture
TEM
Size and Shape Transmission Electron Microscopy (TEM),
SEM,DLS
Rheology Brookfield Viscometer
Conductivity Conductivity Meter
Zeta Potential Zetasizer
pH pH Meter
Drug Release
Studies
Franz Diffusion Cells
Physical Stability
Study
Ultracentrifuge
22
EVALUATION
23. In Vitro Drug Permeation Studies
• Determination of permeability coefficient and flux
– Excised human cadaver skin from the abdomen can be obtained
from dead who have undergone postmortem not more than 5
days ago in the hospital. The skin is stored at 4C and the
epidermis separated.
– The skin is first immersed in purified water at 60C for 2 min and
the epidermis then peeled off.
– Dried skin samples can be kept at -20C for later use.
– Alternatively the full thickness dorsal skin of male hairless mice
may be used.
– The skin shall be excised, washed with normal saline and used.
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24. – The passive permeability of
lipophilic drug through the skin is
investigated using Franz diffusion
cells with known effective
diffusional area.
– The hydrated skin samples are
used. The receiver compartment
may contain a complexing agent
like cyclodextrin in the receiver
phase, which shall increase the
solubility and allows the
maintenance of sink conditions in
the experiments.
– Samples are withdrawn at regular
interval and analyzed for amount
of drug released.
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Fig. Franz diffusion cell
25. • Stability Studies
– The physical stability of the microemulsion must be determined
under different storage conditions (4, 25 and 40 °C) during 12
months.
– Depending on different regulatory agency requirement it’ll vary
according to them.
– Effect of surfactant and their concentration on size of droplet is
also be studied.
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26. References:
• Berry, natasha, "development and stability of microemulsions as carriers
for nutraceuticals" (2011). Theses and dissertations. Paper 679.
• P. J. Sinko, Martin’s Physical Pharmacy & Pharmaceutical Science, 5th
Ed., Wolters Kluwer Press, 2009, Chapter 16.
• Lachman , the theory and practice of industrial pharmacy, 3rd ed.,Varghese
publishing house, 2008, chapter 17.
• The science and practice of pharmacy 21st edition vol-1 remington 2005
pg.No.-315,316,763 published by wolters kluwer health(india) pvt.Ltd.,
New delhi.
• Microemulsion-based media as novel drug delivery systems
www.Elsevier.Com/ locate / drugdeliv advanced drug delivery reviews 45
(2000) 89–121
• “Emerging trend of microemulsion in formulation and research”
international bulletin of drug research., 1(1): 54-83 54
• Michael e aulton, “the design and manufacture of medicines”, elsevier
publisher,third edition(2007)
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