Micro Emulsion 354s4s

Seminar on

MICRO-EMULSI

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Presented by : Nazeer Hasan M.PHARMACY (Industrial Pharmacy) Department of pharmaceutics. Delhi Pharmaceutical Science and Research University (DPSRU).

● HISTORICAL BACKGROUND ● INTRODUCTION ● COMPOSITION ● ADVANTAGES

& DISADVANTAGES ● METHOD OF PREPARATION ● APPLICATIONS

● The Microemulsion concept was introduced

as early as 1940s by Hoar and Schulman who generated a clear single-phase solution by titrating a milky emulsion with hexanol. ● Schulman

and

subsequently microemulsion

co-worker coined the

(1959) term

● The microemulsion definition provided by

Danielson and Lindman in 1981 will be used as the point of reference.

•Modern colloidal drug delivery system •Micro emulsions are clear, transparent, thermodynamically stable dispersions of oil and water, stabilized by an interfacial film of surfactant frequently in combination with a co-surfactant. •Diameter - 10-200 nm.

MICRO-EMULSI

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Microemulsions are mono-dispersed spherical droplets (diameter < 100 nm) of water in oil or oil in water, with presence of surfactants and co-surfactants, as seen in these vials.

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Cont…….

● In this type of system, the two liquids tend to separate

out in two layers. ● And to avoid this, a third substance called as an emulsifier is added, act by: ● they tend to adsorb at interface, where they can fulfill

their dual affinity with hydrophilic groups located in aqueous phase and hydrophobic groups in oil or air. ● they reduce the mismatch with solvent through a specific kind of aggregation process known as micellization

MAJOR GOALS • To delivery of hydrophilic as well as lipophilic drug as

drug carriers because of its • improved drug solubilization capacity, • long shelf life, • easy of preparation and • improvement of bioavailability.

EMULSION Vs MICRO EMULSION: Shape

Macro emulsion

Micro emulsion

EMULSION Vs MICRO EMULSION: Size

MACRO EMULSION Vs MICRO EMULSION FEATURES

MACRO EMULSION

MICRO EMULSION

DEFINITION

Emulsions consist of roughly spherical droplets of one phase dispersed into the other

They constantly evolve between various structures ranging from droplet like swollen micelles to bi continuous structure.

DROPLET SIZE

1 – 20 µm.

10 – 100 nm.

APPEARANCE Most emulsions are opaque (white) because bulk of their droplets is greater than wavelength of light and most oils have higher refractive indices than water.

Microemulsions are transparent or translucent

FEATURES

MACRO EMULSION

MICRO EMULSION

PHASES

Two

One

STABILITY

Stable but coalesce finally

More thermodynamically stable than macroemulsions

PREPARATION

Require intense agitation for Generally obtained by gentle their formation. mixing of ingredients.

SURFACTANT CONCENTRATION

2-3 % Weight

6-8% by weight

MACROEMULSION Vs MICRO EMULSION

ADVANTAGES ● ● ● ● ● ●

thermodynamically stable require minimum energy for formation. Ease of manufacturing and scale-up Improved drug solubilization and bioavailability. drug targeting and controlled release The formation of micro emulsion is reversible. They may become unstable at low or high temperature but when the temperature returns to the stability range, the micro emulsion reforms. ● The use of micro emulsion as delivery systems can improve the efficacy of a drug, allowing the total dose to be reduced and thus minimizing side effects.

DISADVANTAGES ● Use of a large concentration of surfactant and co-

surfactant necessary for stabilizing the nanodroplets. ● Limited solubilizing capacity for high-melting substances ● The surfactant must be nontoxic for using pharmaceutical applications ● Micro emulsion stability is influenced by environmental parameters such as temperature and pH. These parameters change upon micro emulsion delivery to patients.

Theories of Microemulsion formation Solubilization • Packing ratio & P theory • V/a*l

Thermodynamic • ∆G=−ve theory • ∆G= γ ∆G

Mixed Film theory

• Complex film formation at interface • Due to co-surfactant. 16

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Oil

∆Gm = free energy change for microemulsion formation ∆G1 = free energy change due to increase in total surface area ∆G2 = free energy change due to interaction between droplets ∆G3 = free energy change due to adsorption of surfactant at the oil/water interface from bulk oil or water ∆S = increase in entropy due to dispersion of oil as droplets 17

Why are microemulsions thermodynamically stable? ΔGm

ΔGm > 0 for C & D

D

emulsion formation

C R*

B

ΔGm*

R

A

ΔGm* < 0 for A & B in certain Rrange ↓ microemulsion formation in that R range Microemulsions form spontaneously only when IFT is small. (order of 10-3 mN/m)

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Formation of Microemulsion ● Micro emulsion is formed

when ● the interfacial tension at

the O/W interphase are brought very low level. ● The interfacial tension is kept highly flexible and fluid.

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METHODS Phase Titration Method Spontaneous emulsification method depicted with the help of phase diagrams

Phase Inversion Method •occurs upon addition of excess of the dispersed phase or in response to temperature • These methods make use of changing the spontaneous curvature of the surfactant. •changing the temperature of the system, forcing a transition from an o/w microemulsion at low temperatures to a w/o microemulsion at higher temperatures 23

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W/O micro-emulsions • During preparatoin firstly Reverse micelles forms, to minimise S. free energy • They are dynamic i.e. micelles frequently collide via random Brownian motion

Malik M.A. et al, Arabian Journal of Chemistry (2012) 5, 397–417

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O/W micro-emulsions • The charged head group of the microemulsion droplets is the driving force for producing O/W micro-emulsion • This also increases Temperature stability • can be used as carriers for a wide number of organic compounds

Malik M.A. et al, Arabian Journal of Chemistry (2012) 5, 397–417

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Bi-continous micro-emulsions • • • •

Water and oil both are continuous phases Amount also comparable It is like sponge Encountered in microemulsions, in mesophases, and even in relatively dilute surfactant solutions • Indicated by the average mean curvature zero • May also exist as hexagonal liquid crystal structure

Malik M.A. et al, Arabian Journal of Chemistry (2012) 5, 397–417

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Factors affecting micro emulsion formation ● Packing ratio ● Property of surfactant ● Property of oil phase ● Temperature ● Chain length ● Type and nature of cosurfactant

APPLICATIONS

Pharmaceutical applications of microemulsions ● Increase bioavailability of

drugs poorly soluble in water ● Topical drug delivery systems

Preparation of nanoparticles from microemulsion precursors

● Oral drug delivery ● Ocular drug delivery ● Pulmonary drug delivery ● Transdermal drug delivery ● Parenteral drug delivery ● For solubilization of drug ● In biotechnlogy ● others

Oral drug delivery ● Advantages of microemulsions: ● increased absorption ● improved clinical potency ● decreased drug toxicity ● Ritchel et.al(1990) studied the absorption of

cyclosporine (potent, cyclic endekapeptide). ● Poor bioavailability

● 2 w/o microemulsion-sorbitol ester polyoxyethylene

glycolmonoether. LMW alcohol, fatty ester and water.

Topical drug delivery ● Microemulsions may enhance transdermal drug delivery primarily by the following effects: ● Micro emulsions can exhibit a high solubilization capacity for both lipophilic and hydrophilic drugs, thus more drug can be loaded into the microemulsion, which increases the concentration gradient across the skin without depletion. ● The reservoir effect of the internal phase maintains a constant driving force of drug from the external phase to the skin and prolongs absorption. Since the diffusion of the drug into the skin only occurs from the external phase of the micro emulsion, the internal phase continually supplies drug to the external phase so that it remains saturated with the drug.

Ocular and intranasal drug delivery ● For the treatment of eye diseases, drugs are essentially

delivered topically. O/W microemulsions have been investigated for ocular istration, to dissolve poorly soluble drugs, to increase absorption and to attain prolong release profile. ● Hasse and keipett(1997) prepared microemulsion containing pilocarpine were formulated using lecithin,PG and PEG 200 as cosurfactant and IPM as oil phase. The formulation had low viscosity with refractive index leading to ophthalmic application

Parenteral Drug Delivery ● Parenteral istration (especially via the intravenous route) of drugs with ● limited solubility is a major problem ● extremely low amount of drug actually delivered to a targeted site. ● Microemulsion formulations have distinct advantages over macroemulsion systems when delivered parenterally because of ● the fine particle microemulsion is cleared more slowly than the coarse particle emulsion and, therefore, have a longer residence time in the body. Both O/W and W/O microemulsion can be used for parenteral delivery.

Conclusion ● Microemulsions are optically isotropic and

thermodynamically stable liquid solutions of oil, water and amphiphile. ● Microemulsions are readily distinguished from normal emulsions by their transparency, low viscosity and more fundamentally their thermodynamic stability. ● Drug delivery through microemulsions is a promising area for continued research with the aim of achieving controlled release with enhanced bioavailability and for drug targeting to various sites in the body.

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