INTRODUCTION:

The term microemulsion, also called as transparent emulsion, swollen micelle, micellar solution, and solubilized oil, was first used by Jack H. Shulman in 1959¹. Microemulsions are defined as thermodynamically stable, transparent (translucent) dispersions of oils and water that are stabilized by an interfacial film of surfactant molecules. The surfactant may be pure, a mixture, or combined with a cosurfactant such as a medium- chain alcohol (e.g. butanol, pentanol). These homogenous system, which can be prepared over a wide range of surfactant concentrations and oil to water ratio (20-80%), are all fluid of low viscosity. Microemulsions are readily distinguished from normal emulsion by their transparency, their low viscosity, and more fundamentally their thermodynamic stability and ability to form spontaneously².

Microemulsion systems consisting of at least 30% of oil, 1 to 30% of non-ionic surfactant system having a hydrophilic lipophillic balance, HLB, comprised between 9 and 18, 20% of co-solvent and at least 30% of water, can form spontaneously and are therefore thermodynamically stable. For this reason, microemulsion systems theoretically have an infinite shelf life under normal conditions in contrast to the limited life of macroemulsions. In addition, the size of the droplets in such microemulsions remains constant and ranges from 100-1000 A⁰(10-100 nm), and has very low oil/water interfacial tension. Because the droplet size is less than 25% of the wavelength of visible light, microemulsions are transparent^3,4.

Three distinct microemulsion solubilization systems that can be used for drugs are as follows:
1. Oil in water.
2. Water in oil.
3. Bi-continuous microemulsions.

In all three types of microemulsions, the interface is stabilized by an appropriate combination of surfactants and/or co-surfactants⁶.

Fig. 1: (a) oil-in-water (b) bicontinuous (c) water-in-oil microemulsion⁵.

Theory of microemulsion

Three theories proposed for microemulsion formation are:

· Interfacial or mixed film theory

· Solublization theory

· Thermodynamic theory

Fig. : 2 - A hypothetical pseudo-ternary phase diagram of an oil / surfactant /water system. Within the phase diagram, existence fields are shown where conventional micelles, reverse micelles or water-in- oil (w/o) microemulsions and oil-in-water microemulsions are formed along with the bicontinuous microemulsions⁵.

For microemulsion formation the free energy gain have considered to be derived from:

· The extent to which surfactant lowers the interfacial tension between the two phases.

· The change in entropy of the system.

The interfacial tension in the presence of excess surfactant and cosurfactant is very small and close to zero. The parameter λA reflects the surface area of small drops and is very large. The term λA contributes to the destabilization effect of the microemulsion, but it becomes very small with the decrease in the interfacial tension.

In contrast the term T∆S reflects the change in the entropy of the microemulsion, the effective dispersion entropy, as a result of the formation of very small droplets and is very significant. T∆S is also significantly large owing to the mixing of one phase into the other and the formation of an enormous number of droplets.

Hence the term, ∆G = λA – T∆S in microemulsion is always negative.

Careful selection of the surfactant and the nature of the two phases are made. So that the interfacial tension will always be close to the zero. The surfactant chose for particular oil must:

· Lower the interfacial tension to a very low value to aid dispersion process during the preparation of the microemulsion.

· Be of the appropriate hydrophilc-lipophilc character to provide the correct curvature at the interfacial region for the desired microemulsion type O/W, W/O or bicontinuous.

· Provide a flexible film that can readily deform around small droplets.

Phase behavior:

It should be noted that not every combination of components produce microemulsion over the whole range of possible composition, in some instances, the extent of microemulsion might be very limited. At low surfactant concentration, there are certain phases exist in equilibrium. These phases are referred to as Winsor phases. They are:

1. Winsor I (W I): With two phases, the lower (o/w) microemulsions phase in equilibrium with upper phase.

2. Winsor II (W II): Two phases, the upper microemulsion phase (w/o) in equilibrium with excess water.

3. Winsor III (W III): With the three phases, middle microemulsion phase (o/w, w/o, bicontinuous) in equilibrium with upper excess oil and lower excess water.

4. Winsor IV (W IV): In single phase, with oil, water and surfactant homogenously mixed.

Advantages of Microemulsion Based Systems:⁷

· Microemulsions are thermodynamically stable system and the stability allows self-emulsification of the system.

· A property of microemulsions doesn’t depend on the process followed.

· They can solubilize both hydrophilic and lipophillic drugs including drugs, which are relatively insoluble in both aqueous and hydrophobic solvents. Hence they are called as supersolvents. This property of microemulsions is due to the formation of microdomains of different polarity within the same single phase system.

· The dispersed phase hydrophilic or lipophillic can behave as a reservoir of lipophillic and hydrophilic drugs respectively.

· The drug release across a membrane follows pseudo zero order kinetics and it depends on the volume of the dispersed phase, partition of the drug and transport rate of drug across membrane.

· Microemulsions can be sterilized by filtration due to their small size.

· Same microemulsion can carry both lipophillic and hydrophilic drug.

· Microemulsions are easy to prepare and require no significant energy contribution during preparation.

· Microemulsions improve the efficacy of a drug, allowing the total dose to be reduced.

Disadvantages of Microemulsion Based Systems:⁸

· Large concentration of surfactant and co-surfactant is necessary.

· Limited solubilizing capacity for high-melting substances.

· The surfactant must be nontoxic for using pharmaceutical applications.

· Microemulsion stability is influenced by environmental parameters such as temperature and pH. These parameters change upon microemulsion delivery to patients.

Calculation of HLB value:⁹

The definition of the HLB value for polyol fatty acid esters is given by
HLB=20*(1-S/A)………………I

Where,

S= Saponification number of the ester,

A= Acid number of the acid recovered
for a group of emulsifiers, the hydrophilic content of which comprises only ethylene oxide units, applies
HLB=E/5………………………II
where
E=weight content of ethylene oxide (in %) in the total molecule.
Emulsifiers having HLB values of 6-8 are in general W/O emulsifiers, and those having HLB values of 8-18 are in general O/W emulsifiers.

Fig.: 3 - A hypothetical ternary phase diagram representing three components of the system (Water, emulsifier (E), and oil) as three axis of an equilateral triangle³. Different compositions of the formulation result in the formation of different phase structures: normal micellar solution, inverted micellar solution, macroemulsions or emulsions, o/w microemulsions, w/o microemulsions, and various transition phases represented by cylinders and lamellae structures.

PHASE DIAGRAMS¹⁰:

The microemulsion region is usually characterized by constructing ternary-phase diagrams. Three components are the basic requirement to form a microemulsion: an oil phase, an aqueous phase and a surfactant. If a cosurfactant is used, it may sometimes be represented at a fixed ratio to surfactant as a single component, and treated as a single "pseudo-component". The relative amounts of these three components can be represented in a ternary phase diagram. The three components composing the system are each found at an apex of the triangle, where their corresponding volume fraction is 100%. Moving away from that corner reduces the volume fraction of that specific component and increases the volume fraction of one or both of the two other components. Each point within the triangle represents a possible composition of a mixture of the three components or pseudo-components. These points combine to form regions with boundaries between them, which represent the "phase behavior" of the system at constant temperature and pressure.

Method of preparation of microemulsion¹¹:

A method of forming a microemulsion comprises following steps:

· Forming a mixture of liquids so as to produce a microemulsion-forming liquid system.

· Dividing liquid mixture into at least two mixture streams.

· Pressurizing each of liquid streams to a pressure of at least 4000 psi.

· Ejecting each of said pressurized streams through a corresponding nozzle, at a velocity of at least 40 meters/second, into a low-pressure zone filled with said mixture.

· Mixture streams impinge upon one another in said low pressure zone.

· These create a turbulent jet interaction of said streams along a common boundary.

· The microemulsion includes disperse phase droplets having a diameter no greater than about 1 μm and removing formed microemulsion from low pressure zone.

SOLUBILIZATION OF POORLY SOLUBLE DRUGS³:

Solutions, emulsions, Microemulsion, and micelles

The solute–solvent interactions can be qualitatively as well as quantitatively changed to improve the drug solubility. For example, pH can be adjusted with buffers to increase ionization of a weakly acidic or a weakly basic drug, resulting in higher ion dipole solute–solvent interactions. Co-solvent addition reduces the dielectric constant of water and facilitates hydrophobic interactions of drug molecules with the solvent system.

Mechanism of enhancing solubility

In the presence of a significant amount of oil, surfactants concentrate on the oil/water interface forming:

· emulsions, wherein the drug is solubilized in the internal oil phase.

· When the oil content is low, minute oil-entrapped surfactant globules are produced, which are known as swollen-micelles or microemulsions.

· Drug may be solubilized in the oily core and/or on the interface of these structures.

· The predominant location of drug solubilization depends on its hydrophobicity and interactions with the surfactant and/or cosurfactant.

· Microemulsions differ from micelles in the presence of oil and from emulsions in the amount of the dispersed phase.

· Microemulsions often require a cosolvent and/or cosurfactant to facilitate their formation.

· Both microemulsions and micelles are useful for preparing aqueous solutions of hydrophobic drugs.

· The physical nature of these systems, mechanism of drug entrapment, as well as the physicochemical interactions of constituents determines their drug solubilization capacity and physical stability during storage and upon dilution.

Fig.: 4 - Schematic representation of the most commonly encountered self-association structures in water, oil or a combination thereof⁵.

Drug entrapment and structure:

· Location of the solubilized drug in microemulsion systems depends on the hydrophobicity and structure of the solute.

· The maximum amount of solubilized hydrophobic drug is dependent on the curvature of the interface.

· Surfactant layer on the interface has a positive curvature towards the dispersed phase, which is determined both by the relative volume of dispersed phase and the spontaneous curvature of surfactant molecules.

· Entrapment of drug molecules in the interface is facilitated, leading to higher drug loading capacity, if the spontaneous curvature is lower than the actual curvature.

· Using phase equilibrium analyses, interfacial partition coefficient of the solute depended weakly on surfactant concentration and did not depend on solute concentration and aggregate geometry.

· It depended strongly on the factors that affect surface pressure or bending moment of the surface film, e.g., solvent type and external electrolyte type and concentration.

· The presence of the solute itself affects the system, depending on the nature of the solute and the surfactant. The phenomenon of drug solubilization at the interface affects not only drug loading capacity but also drug precipitation upon dilution.

Solubilization capacity in microemulsions:

Microemulsion systems are often able to solubilize higher amount of drug than its individual components. This higher capacity for solubilization was attributable to the interfacial locus of drug solubilization, which has higher solubilization capacity than the core. Higher solubilization capacity at the interface is a function of drug–surfactant interactions leading to drug association at the interface. These interactions depend on the hydrophobicity, functional groups, and shape of the drug and the surfactant/ cosurfactant. The solubilization capacity progressively decreases upon aqueous dilution, as the micellar system passes through swollen w/o reverse micelles, to bicontinuous phase, to o/w microemulsion system. Evaluation of drug solubilization capacity at different dilution levels allows the formulator to define the appropriate dilution range for a given formulation with minimum likelihood of drug precipitation.

CHARACTERIZATION OF MICROEMULSIONS:

It involves the physical and chemical tests related to oral liquid dosage forms e.g. assay, uniformity of content, stability of the active (impurities), appearance, pH, viscosity, density, conductivity, surface tension, size and zeta potential of the dispersed phase, etc. with respect to the effect of the composition on physical parameters .

Advance studies to characterize microemulsion:

· Differential scanning calorimetry (DSC)

· Polarization microscopy

· Photon correlation spectroscopy (PCS) and total-intensity light scattering (TILS) techniques.

· Static light scattering (SLS), dynamic light scattering (DLS), and small-angle neutron scattering (SANS).

· Self-diffusion nuclear magnetic resonance (SD NMR) and small-angle X-ray scattering (SAXS).

· Crosspolarizers study.

· Accelerated tests such as centrifugation or freeze thaw cycles.

· In addition, this dosage form is tested to evaluate the tendency for drug precipitation or crystallization by physical observation upon undisturbed storage at room temperature and refrigerated conditions upon dilution with water to form o/w microemulsions, which can be done by dropwise addition, static serial dilution, or dynamic injection.

Fig. : 5 - Mechanism of phase inversion of a water-in-oil microemulsion¹⁶.

· Modified in vitro tests can be used for more accurate assessment of tendency for drug precipitation.

· Saturation solubility evaluation.

· Phase inversion temperature (PIT) method.

· Drug release rate studies using Franz diffusion cell or using US Pharmacopeial methods for dissolution testing.

MICROEMULSION STRUCTURE¹²:

The simplest representation of the structure of microemulsion is the droplets model in which microemulsion droplets are surrounded by interfacial film consisting of both surfactant and cosurfactant molecules. The orientation of the amphiphiles will differ in O/W and W/O microemulsion. In O/W system the hydrophobic portion of molecules reside in the dispersed oil droplets with the hydrophilic groups protruding in the continuous phase, while the opposite is true for W/O microemulsion. The structures of microemulsion containing almost equal amount of oil and water with high surfactant content are not well understood. Microemulsions are highly dynamic in nature due to the thermal fluctuation interfaces. Although microemulsion droplets are thermodynamically stable, they constantly undergo coalescence, breakdown and deformation process resulting in thermally induced size and shape fluctuation of those droplets.

Microemulsion structure characterization:¹³

It requires macroanalytical tools such as viscosity, conductivity, dielectric and differential scanning calorimetry(DSC), together with scattering advanced techniques (DLS, SAXS, SANS) and spectroscopic advanced methods (HR-NMR, PSEG-NMR) and electronic microscopy ( TEM and cryo- TEM) .

Small angle scattering:

Small angle X-ray scattering (SAXS) and small angle neutron scattering (SANS), probe the pertinent colloidal length scales of 1 to 100 nm and therefore are used to obtain information on the size, shape, and internal structure of colloidal particles.

Figure: 6⁴⁹ Schematic ternary phase diagram of water–oil–surfactant mixtures representing Winsor classification and probable internal structures. It represents L1, a single phase region of normal micelles or oil-in-water (o/w) microemulsion; L2, reverse micelles or water-in oil (w/o) microemulsions; D, anisotropic lamellar liquid crystalline phase. The microemulsion is marked by µE, oil by O and water by W.

Light scattering:

These measurements are often routinely used to determine droplet sizes in microemulsions. Awareness of the shape of the droplets prior to analysis of the scattering data (e.g. with SANS or SESANS) is necessary because commercial instruments assume spherical shapes. It is recommended to parallel DLS measurements with static light scattering observations as occasionally the micelles scatter so strongly that the oil droplet peak becomes obscured in the distribution function¹⁴. Andrej Jamnik et.al. described Small-angle X-ray scattering technique used to study the structural properties of the quaternary microemulsion¹⁵. Constantinides et.al. studied effect of dilution on microemulsion formulation with excess of the dispersed (aqueous) phase to induce phase inversion and generate oil-in-water (o/w) and/or water-in-oil-in-water (w/o/w) emulsions¹⁶.

Cryo-Transmission electron microscopy:

Cryo-Transmission electron microscopy (cryo-TEM) has emerged as a unique and powerful method for structural analysis of a wide range of biological macromolecules and complexes including microemulsions.

Self-diffusion Coefficients from PGSE-NMR:

NMR diffusion measurements are potentially a valuable tool for probing the conformation and state of molecules within their environment¹³. Yu chan et.al studied the microemulsions characterization by transmission electron microscopy (TEM), X-ray diffraction (XRD), and energy dispersive X-ray analysis (EDX)¹⁷. Bester Roga et.al. assessed microemulsion type and structure by measuring density and surface tension, and by viscometry, electric conductivity, differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS), and the degree of agreement between the techniques. A model based on monodisperse hard spheres adequately fits the SAXS data in W/O microemulsions predicting, depending on composition, elongated or spherical droplets. DSC detects the degree of water interaction with surfactants thus identifying the type of microemulsion. These techniques can be used to determine type and structure of such microemulsion systems could enable partitioning and release rates of drugs from microemulsions to be predicted¹⁸.

Effect of Physico-Chemical Properties on Microemulsion Formulation:

Various physical and chemical properties of oil, surfactant and co-surfactant effect the formation of microemulsion. Ljiljana Djekic et. al. studied the influence of CoSurfactants and oils on the formation of pharmaceutical microemulsions, based on PEG-8 caprylic/capric glycerides. They suggest that Low molecular volume oils, such as fatty acid esters and triglycerides with medium chain lengths are preferred instead of high molecular volume oils. The chemical structure of oil is also very important factor in microemulsion formation²⁰.

MICROEMULSION APPLICATION IN FORMULATION:

Controlled release solid state microemulsion:

Microemulsions are used to form the controlled release products, prepared by dispersing microemulsion in a carrier and mixed to be homogeneous. The solvent is then removed by such a method as evaporation under reduced pressure, spray drying etc., resulting in solidification and controlled release of drug from microemulsions²¹.

Nanocapsules from w/o microemulsions:

The advantages of preparing PECA nanocapsules by interfacial polymerization of water-in-oil microemulsions over other methods may have implications with regards to maintaining the stability and achieving efficient entrapment of certain bioactive, particularly proteins and peptides. Various physico-chemical characteristics of the nanocapsules like size, wall thickness, polymer molecular weight, and release rate can be controlled by manipulation of some of the formulation variables such as the amount of monomer used, the water weight fraction of the aqueous component of the microemulsion and the pH²². Anju graf et.al. also mentioned the insulin nanoparticles prepared by interfacial polymerization technique from w/o microemulsions²³.

Nanosuspension:

Michele trotta et.al describes the formulation of griseofulvin nanoparticles from water dilutable microemulsions. This nanosuspension can be prepaered by microemulsion-diffusion technique using pharmaceutically acceptable solvents, such as butyl lactate, using optimized formulations; griseofuvin nanoparticles below 100 nm with low polydispersity were obtained. Dissolution rates of griseofulvin particles obtained by the solvent diffusion procedure were higher than that commercial product²⁴.

APPLICATION IN DRUG DELIVERY:

Parentral application:

Microemulsions are used in parentral drug delivery due to their small particle size and low viscosity nature. Chong-Kook Kim et. al. prepared Phospholipids-based microemulsions using ethanol as a cosolvent by the spontaneous emulsification process. The plasma concentrations of flurbiprofen following the intravenous administration of the microemulsion were similar to those following commercial Lipfen. However, the T_1/2, AUC and MRT of flurbiprofen-loaded microemulsion were significantly increased. This microemulsion could also reduce uptake into RES-rich organs, which is one of the characteristics of this particular drug carrier system, due to the increase in the surface hydrophilicity of the microemulsion²⁵. Chong-Kook Kim et. al. also study a parentral formulation of ATRA . This formulation overcomes its solubility limitation by utilizing phospholipid-based microemulsion system as a carrier²⁶. Jian Ping Zhou et. al. studied the use of chitosan in the microemulsion formulations . Chitosan might significantly increase the brain uptake of nobiletin, and simultaneously reduce the concentration of drug delivered to the heart and kidney. These results indicate that chitosan-ME may be advantageous for drug accumulation in the brain and may also help to reduce systemic toxicity. The prolongation of circulation time of nobiletin in chitosan-ME may play an important role in the drug brain uptake²⁷.

Dermal application:

Dermal formulations have the advantage over oral formulation in avoiding the first pass metabolism, hence improved bioavailbility. Ljiljana Djordjevic et. al. studied Microemulsion for delivery of an amphiphillic drug for dermal application, drug effect on vehicle microstructures and drug release kinetics²⁸. Jayne Lawrence et.al. formulated gelatin stabilized microemulsion-based organogel and also studied their rheology and application in iontophoretic transdermal drug delivery²⁹. Urtti et.al. formulated estradiol microemulsions for topical delivery. Microemulsion formulations increased estradiol flux 200–700-fold over the control, but permeability coefficients were decreased by 5–18 times. The superior transdermal flux of estradiol was due to 1500-fold improvement in solubilization of estradiol by microemulsions. The results suggest that microemulsions are potential vehicles for improved topical delivery of estradiol³⁰.

Oral formulation:

Microemulsion formulations have superior bioavailability in comparison to other oral formulations such as hydro-alcoholic solution, suspension and coarse emulsion. Sylvie Crauste-Manciet et.al. explained the enhancement of oral bioavailability of cefpodoxime proxetil by formulating the oil in water oral submicron emulsion³¹. Kohsaku Kawakamia et. al. worked on microemulsion formulations, which are known to improve the bioavailability of poorly soluble drugs. Nitrendipine was used as a poorly soluble model drug, and its absorption was enhanced significantly by employing the microemulsion formulations compared to a suspension or an oil solution³². Chong-Kook Kim et.al. described the enhancement of bioavailability of cyclosporine A by using o/w microemulsion. This enhancement is thought to be due to the combination of factors including the drug solubilization effect and the increase of drug permeability through the intestinal membrane. In other words, the bioavailability of drugs loaded in microemulsions was dependent on the physicochemical properties of drug and o/w microemulsion³³. Zhang et.al. formulated the earthworm fibrinolytic enzyme (EFE-d) loaded w/o microemulsion system consisting of Labrafac CC, Labrasol/Plurol Oleique CC 497 and saline. Compared with the control solution, an obviously increased absorption of EFE-d protein and enhanced pharmacological activity are observed in rats after intraduodenal or oral administration of the w/o microemulsion vehicle. Additionally, there are no any signs of damage in intestinal mucosa when treated with w/o microemulsion for multiple-doses³⁴. Microemulsions are also shown to enhance the bioavailability and the solubility of orally administered poorly soluble acyclovir³⁵. The performance of dioctyl sodium sulfosuccinate (aerosol OT) in the development of a pharmaceutically acceptable, stable, self-emulsifying water continuous microemulsion with high dilution efficiency was assessed for oral drug delivery³⁶.

SMEDDS:

SMEDDS contain the non-aqueous components of microemulsions and readily disperse upon dilution in aqueous phase with mild agitation to form microemulsions. SMEDDS are often preferred over microemulsion formulations for hydrolytically sensitive drugs and their low volume enables packing into soft gelatin capsules for oral administration. Self-microemulsifying drug delivery system (SMEDDS) for oral bioavailability enhancement of a poorly water soluble drug, Simvastatin was studied by Sun Hang Choc et.al.³⁷. Hiroshi Araya formulated the novel O/W microemulsion formulation which enhances the oral bioavailability by raising the solubility of poorly water soluble compounds. The improving effect of the solubility by this O/W microemulsion was examined for about 11 kinds of poorly water soluble compounds, such as Ibuprofen, Ketoprofen, Chloramphenicol, Testosterone, Tolbutamide, Tamoxifen, Disopyramide and other new compounds³⁸.

Nasal microemulsion:

Jiang et.al. studied the formulation of nimodipine loaded microemulsion for intranasal delivery and also their targeting efficiency to brain. The results show that after a single intranasal administration of this preparation at a dose of 2 mg/kg, the plasma concentration peaked at 1 h and the absolute bioavailability was about 32%. The uptake of NM in the olfactory bulb from the nasal route was three folds, compared with intravenous (i.v.) injection. The ratios of AUC in brain tissues and cerebrospinal fluid to that in plasma obtained after nasal administration were significantly higher than those after i.v. administration³⁹. Intranasal administration of carvedilol through microemulsion formulations may enhance the bioavailability of drug. Formulation of carvedilol into microemulsion enhances the nasal absorption of drug by enhancing the solubility of drug⁴⁰. Botner et.al. formulated insulin microemulsion spray for intranasal delivery⁴¹. Mishra et.al. performed the brain targeting studies on intranasal microemulsions. The pharmacokinetic parameters, drug targeting efficiency (DTE), and direct drug transport (DTP) were derived. Gamma scintigraphy imaging of rat brain following IV and intranasal administrations were performed to ascertain the localization of drug⁴². Nasal treatment with a microemulsion reduces allergen challenge-induced symptoms and signs of allergic rhinitis⁴³. An ethyl laurate-based microemulsion system with Tween 80 as surfactant, propylene glycol and ethanol as cosolvents was developed for intranasal delivery of diazepam. Nasal absorption of diazepam from this microemulsion was found to be fairly rapid. At 2 mg/kg dose, the maximum drug plasma concentration was arrived within 2–3 min, and the bioavailability (0–2 h) after nasal spray compared with intravenous injection was about 50%⁴⁴.

Other application of microemulsion:

Microemulsions in enhanced oil recovery , as fuels, as coatings and textile finishing, as lubricants, cutting oils and corrosion inhibitors, in detergency, in cosmetics, in agrochemicals, in food, in pharmaceuticals, in environmental remediation and detoxification, in analytical applications, Microporous media synthesis (microemulsion gel technique), as liquid membranes, in biotechnology (Enzymatic reactions in microemulsions, Immobilization of protein in microemulsion, Microemulsions for bioseparations⁴⁵.

Microemulsions are also used in cosmetic industry, such in the preparation of shampoo and Aerosol microemulsion ^46,47. The products of microemulsions can be used to coat the pore walls, i.e., to coat the encompassing structure that defines the pores⁴⁸. Microemulsions not containing any pharmaceutical agent are useful for the prevention of symptoms in mammals⁴⁹. The microemulsion can be used especially in foodstuffs, in pharmaceutical preparations and in cosmetics⁵⁰.

Miscellaneous:

Ljiljana Djordjevic et. al. studied the influence of both formulation parameters and vehicle structure on in vitro release rate of amphiphilic drug diclofenac diethylamine (DDA) from microemulsion⁵¹. Trotta et. al. studied the Phase behaviour of microemulsion systems containing lecithin and lysolecithin as surfactants⁵². Ruth SH et. al. studied the Phase behaviour and particle size analysis of oil-in-water phospholipid microemulsions⁵³.

CONCLUSION:

Microemulsion is a system where the drugs are made solubilized by using the large amount of surface active agents. Hence in case of the lipophillic drugs, it can also increase the solubility of the drug. The dosage form like Microemulsions provides a helpful solution for the stability as well as the bioavailability problems. The microemulsions prepared by using oil, surfactant, Co-surfactant was stable and clear for acceptable period of time. It is also a very useful technique of administration of drug when rapid access of drug is necessary.

Microemulsion is proven possible to formulate preparations suitable for most routes of administration, in addition to able to protect labile drug, controlled drug release, increase drug solubility, increase bioavailability and reduce patient variability. There is still however a considerable amount of fundamental work characterizing the Physico-chemical behaviour of microemulsions that needs to be performed before they can live up to their potential as multipurpose drug delivery vehicles.

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Received on 25.02.2009 Modified on 22.07.2009

Research J. Pharm. and Tech.2 (3): July-Sept. 2009,;Page 441-448

Sr. No.	Microemulsion	Emulsion
1.	Forms spontaneously, without mechanical work	Requires considerable energy input for its preparation
2.	Thermodynamically stable but kinetically unstable.	Possess kinetic stability, but thermodynamically unstable
3.	Domains of disperse phase are typically less than 140 nm and relatively uniform in size,	Possess droplets of varying size
4.	Transparent	Cloudy.

Sr. No.	Microemulsion	Nanoemulsion
1.	Thermodynamically stable	Kinetically stable
2.	Possess long-term stability	Do not possess long-term stability
3.	Requires a lower surfactant concentration	20 wt% surfactant typically needed

Advantages of Microemulsion Based Systems:7

4. US Patent 6902756: Transparent high oil loaded microemulsions.

Advantages of Microemulsion Based Systems:⁷