INTRODUCTION:

The design and development of novel drug delivery system with the intention of enhancing the efficacy of existing of drug is an ongoing process in pharmaceutical research. Out of various drug delivery systems that have been developed, one in particular the colloidal drugs delivery system has great potential for achieving the goal in drug targeting. The microemulsion concept was introduced as early as the 1940s by Hoar and Schulman who generated a clear single-phase solution by titrating a milky emulsion with hexanol [1].

They prepared the first microemulsion by dispersing oil in an aqueous surfactants solution and adding an alcohol as a co-surfactant, leading to transparent stable formulation. In 1959, Schulman and co-workers subsequently coined the term microemulsion [2].

Microemulsion is defined as a thermodynamically stable, isotropically clear dispersion of two immiscible liquids, such as oil and water, which is stabilized by an interfacial film of surfactant molecules. Surfactant molecules contain both a polar as well as an apolar group. So they exhibit a very peculiar behavior, firstly, they get adsorbed at the interface, where they can fulfill their dual affinity with hydrophilic groups located in aqueous phase and hydrophobic groups in oil or air. Secondly, they reduce mismatching with solvent by Micellization Process [3]. The dispersed phase typically comprises of small particles or droplets, with a size range of 5 nm-200 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. The microemulsion is formed readily and sometimes spontaneously, generally without high-energy input. In many cases a cosurfactant or cosolvent is used in addition to the surfactant, the oil phase and the water phase [4]. Microemulsions contain definite boundary between oil and water phases at which surfactant is located. Conventional surfactant molecules comprised polar head group region and an apolar tail region. Microemulsions are transparent and structure cannot be observed through an optical microscope. Microemulsions are liquid behave as a Newtonian liquid. They are not very viscous [5].

Table 1: Difference between emulsion and Microemulsions [6]

Property	Emulsion (Macro emulsion)	Microemulsions
Appearance	Cloudy	Transparent
Optical isotropy	Anisotropic	Isotropic
Interfacial tension	High	Ultra low
Microstructure	Static	Dynamic
Droplet size	>500 nm	20-200 nm
Stability	Thermodynamically unstable	Thermodynamically stable and long shelf life
Phases	Biphasic	Monophasic
Preparation	Require a large input of energy	Facile preparation
Cost	Higher cost	Lower cost
Viscosity	High viscosity	Low viscosity with Newtonian behavior
Turbidity	Turbid	Transparent
Surfactant concentration	1-20 %	>10%
Size range	0.5 – 5 μ	<0.1 μ
Molecular packing	Inefficient	Efficient

Advantages of microemulsion system [7-8]

1. These are easily prepared and require no energy contribution during preparation this is due to better thermodynamic stability.

2. The formation of microemulsion is reversible. They may become unstable at low or high temperature but when the temperature returns to the stability range, the microemulsion reforms.

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

4. Microemulsions have low viscosity compared to emulsions.

5. Microemulsions act as supersolvents for drug, can solubilise both hydrophilic and lipophilic drugs including drugs that are insoluble in both aqueous and hydrophobic solvents.

6. Having the ability to carry both lipophilic and hydrophilic drugs.

7. The dispersed phase, lipophilic or hydrophilic (O/W, or W/O microemulsions) can act as a potential reservoir of lipophilic or hydrophilic drugs, respectively.

8. The use of microemulsion as delivery systems can improve the efficacy of a drug, allowing the total dose to be reduced and thus minimizing side effects.

Disadvantages of Microemulsion Systems [9-10]

1. Having limited solubilizing capacity for high melting substances.

2. Require large amount of Surfactants for stabilizing droplets.

3. Microemulsion stability is influenced by environmental parameters such as temperature and pH.

Types of microemulsions [11-13]

Microemulsions are thermodynamically stable, but are only found under carefully defined conditions. According to Winsor, there are four types of microemulsion phases exists in equilibria, these phases are also referred as Winsor phases.

They are,

1. Oil- in- water microemulsion or winsor I

2. Water – in oil microemulsion or winsor II

3. Bicontinuous microemulsion or winsor III

4. Single phase homogeneous mixture or winsor IV

Oil- in- water microemulsion or winsor I:

In Oil-in-water type of microemulsions droplets of oil is surrounded by a surfactant (and may be cosurfactant) film that forms the internal phase distributed in water, which is the continuous phase. This type of microemulsion generally has a larger interaction volume than the w/o microemulsions.

Water - in - oil microemulsion or winsor II:

In Water-in-oil type of microemulsions droplets of water surrounded by a continuous oil phase. These are recognized as “reversemicelles”, where the polar headgroups of the surfactant are facing into the droplets of water, with the fatty acid tails facing into the oil phase. A w/o microemulsion used orally or parenterally may be destabilized by the aqueous biological system.

Bicontinuousmicroemulsion or winsor III:

In bicontinuousmicroemulsion system the amount of water and oil present are similar, In this case, both water and oil exist as a continuous phase. An irregular channel of oil and water are combined, and looks like a “sponge-phase”. Transitions from o/w to w/o microemulsions may pass through this bicontinuous state. Bicontinuous microemulsion, may show non-Newtonian flow and plasticity. These properties make them especially useful for topical delivery of drugs or for intravenous administration.

Single phase homogeneous mixture or winsor IV:

In single phase homogenyeous mixture or winsor IV the oil, water and surfactants are homogenously mixed.

Ingredients of microemulsion [14-16]:

Various ingredients are used in the formulation and development of microemulsions. Mainly oil and surfactants are used in microemulsion they should be biocompatible, non-toxic and clinically acceptable. Main components of microemulsion are

1. Oil phase

2. Aqueous phase

3. Surfactant

4. cosolvent

Oil phase:

Oil is one of the most important components of microemulsion because it can solubilise the required dose of the lipophilic drug and it increases the fraction of lipophilic drug transported via the intestinal lymphatic system. Oil is defined as any liquid having low polarity and low miscibility with water. The examples of such phase are cyclohexane, mineral oil, toulene, & vegetable oil etc.

Aqueous Phase:

Generally the aqueous phase contains hydrophilic active ingredients and preservatives. Sometimes buffer solutions are used as aqueous phase.

Surfactant:

The term surfactant (surface-active-agent) denotes a substance which exhibits some superficial or interfacial activity & used to lower the surface or interface tension. It has affinity for polar & nonpolar solvents. Surfactants are the molecules that contain a polar head group and a polar tail. Surfactant molecules self-associate due to various inter- and intra-molecular forces as well as entropy considerations. For example, when surfactant is mixed with oil and water, they accumulate at the oil/water interface, because it is thermodynamically favorable. The surfactant molecules can arrange themselves in a variety of shapes. They can form spherical micelles, a hexagonal phase, lamellar (sheet) phases, rod shaped micelles, reverse micelles, or hexagonal reverse micelles. At low concentrations of dispersed (internal) phase, spherical, isolated droplets are present in the microemulsions. The various types of surfactants that help in the progressive development of microemulsion system are

· Cationic

· Anionic

· Non-ionic

· Zwitterionic surfactants

· Cationic surfactant

Cationic Surfactants when come in contact with water they come into amphiphiliccation and anion form, most often of halogen type. A very large quantity of this class corresponds to nitrogen compounds such as quaternary ammoniums and fatty amine salts, with one or several long chain of the alkyl type, often coming from natural fatty acids. The most well-known examples from the cationic surfactant class are hexadecyl trimethyl ammonium bromide and didodcecyl ammonium bromide. These surfactants are in general more expensive than anionics.

· Anionic surfactant:

When anionic Surfactants are dissociated in water in an amphiphilic anion, and a cation, which is in general an alkaline metal (Na, K) or a quaternary ammonium. These are the most commonly used surfactants. The anionic charge in these surfactants comes from the ionized carboxyl group. Anionic surfactants account for about 50 % of the world production. Alkali alkanoates, also known as soaps, are the most common anionic surfactants. This is the most well-known type of surfactant when it comes to their shape and function. The three most important anionic groups in all of these surfactants are carboxylate, sulfonate and sulfate groups.

· Non-ionic surfactant:

Non-ionic surfactant is stabilized by dipole and hydrogen bond interactions with the hydration layer of water on its hydrophilic surface. They do not ionize in aqueous solution, because their hydrophilic group is of non-dissociable type, such as phenol, alcohol, ester, or amide. A large proportion of these nonionic surfactants are made hydrophilic by the presence of a polyethylene glycol chain.

· Zwitterionic surfactant:

Zwitterionic surfactants contain both positively and negatively charged groups and form microemulsions by addition of co-surfactants. Phospholipids, such as lecithin, obtained naturally from soybean or egg are common zwitterionic surfactants. Unlike other ionic surfactants, which are somewhat toxic, lecithin which contains diacyl phosphatidylcholine as the major constituent show excellent biocompatibility. Other important class of zwitterionic surfactants is the betaines, such as alkylbetaines, and heterocyclic betaines.

Cosolvent:

It has been observed that single-chain surfactants are unable to reduce the o/w interfacial tension sufficiently to form a microemulsion. The addition of co-surfactants allows the interfacial film to be flexible to take up different curvatures required to form microemulsion over a wide range of excipients. If a single surfactant film is desired, the lipophilic chains of the surfactant should be sufficiently short, or contain fluidizing groups (e.g. unsaturated bonds). Basic co-surfactants are short chain alcohols (ethanol to butanol), glycols such as propylene glycol, medium chain alcohols, amines or acids. The use of co-surfactant is to destroy liquid crystalline or gel structures that come in place of a microemulsion phase.

Method of Preparation [17, 18]:

Two main method are reported for the formulation of microemulsion, these are

1. Phase Inversion Method

2. Phase Titration Method

1. Phase Titration Method:

Microemulsions are prepared by the spontaneous emulsification method (phase titration method) and can be depicted with the help of phase diagrams. Construction of phase diagram is a useful approach to study the complex series of interactions that can occur when different components are mixed. Microemulsions are formed along with various association structures (including emulsion, micelles, lamellar, hexagonal, cubic, and various gels and oily dispersion) depending on the chemical composition and concentration of each component. It is found that as the chain length of the surfactant increased, microemulsions with significant transmittances by visible spectrum can be formed with oils of longer chain lengths. It is also found that different alcohols affect the formation of microemulsions in different ways The understanding of their phase equilibria and demarcation of the phase boundaries are essential aspects of the study. As quaternary phase diagram (four component system) is time consuming and difficult to interpret, pseudoternary phase diagram is often constructed to find the different zones including Microemulsions zone, in which each corner of the diagram represents 100% of the particular component (Fig. 1). The region can be separated into w/o or o/w microemulsions by simply considering the composition that is whether it is oil rich or water rich. Observations should be made carefully so that the metastable systems are not included. For example A mixture of fatty acid and oil is added to a caustic solution to prepare a microemulsion, then after it is titrated with a cosurfactant, an alcohol, until the system turned clear.

Figure 1: Pseudoternary phase diagram of oil, water and surfactant showing microemulsion region.

2. Phase Inversion Method:

Phase inversion of microemulsions occurs upon addition of excess of the dispersed phase or in response to temperature. During phase inversion drastic physical changes occur including changes in particle size that can affect drug release both in vivo and in vitro. These methods make use of changing the spontaneous curvature of the surfactant.

For non-ionic surfactants, this can be achieved by 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 (transitional phase inversion). During cooling, the system crosses a point of zero spontaneous curvature and minimal surface tension, promoting the formation of finely dispersed oil droplets. This method is referred to as phase inversion temperature (PIT) method.

Instead of the temperature, other parameters such as salt concentration or pH value may be considered as well instead of the temperature alone. Additionally, a transition in the spontaneous radius of curvature can be obtained by changing the water volume fraction. By successively adding water into oil, initially water droplets are formed in a continuous oil phase. Increasing the water volume fraction changes the spontaneous curvature of the surfactant from initially stabilizing a w/o microemulsion to an o/w microemulsion at the inversion locus. Short-chain surfactants form flexible monolayers at the o/w interface resulting in a bicontinuous microemulsion at the inversion point.

Theories of microemulsion formulation [19, 20]:

The formulation of microemulsion is based on various theories that effect and control their stability and phase behavior. These theories are

1 Thermodynamic theory

2 Solubilisation theory

3 Interfacial theory

1. Thermodynamic theory:

Formuation and stability of microemulsion can be expressed on the basis of a simplified thermodynamic machanism. The free energy of microemulsion formation can be dependent on the extent to which surfactant lowers the surface tension of the oil–water interface and the change in entropy of the system, thus

G = γ A T S…………………………………… (1)

Where,

G = Free Energy of formation,

γ =Surface Tension of the oil–water interface,

A = Change in interfacial area on microemulsification,

S = Change in entropy of the system which is effectively the dispersion entropy, and

T = Temperature.

It is found that when a microemulsion is formed, A is changed to a large extent due to the large number of very small droplets formed. It is must to know that while the value of γ is positive at all times, it is very small, and is offset by the entropic component. The dominant favorable entropic contribution is the very large dispersion entropy arising from the mixing of one phase in the other in the form of large numbers of small droplets. However, favorable entropic contributions also come from other dynamic processes such as monomer-micelle surfactant exchange and surfactant diffusion in the interfacial layer. When large reductions in surface tension are found by significant favorable entropic change, a negative free energy of formation is achieved. In that case, microemulsification is spontaneous and the resulting dispersion is thermodynamically stable.

2. Solubilisation theory:

The formation of microemulsion is oil soluble phase and water phase by micelles or reverse micelles in micellar gradually become larger and swelling to a certain size range results.

3. Interfacial theory:

The interface mixed-film theory i.e a negative interfacial tension theory, according to this theory the micro-emulsion has been capable to form instantaneous and spontaneously generate a negative interfacial tension in the surfactant and co-surfactant in working together. The film, which may consist of surfactant and cosurfactant molecules, is considered as a liquid ‘‘two dimensional’’ third phase in equilibrium with both oil and water. Such a monolayer could be a duplex film, i.e. giving different properties on the water side and oil side.

Factor affecting formulation of microemulsion system [21]:

Property of surfactant:

Surfactant contains two group lipophilic and hydrophilic groups. Hydrophilic single chain surfactants such as cetylethyl ammonium bromide dissociate completely in dilute solution and have a tendency to form o/w microemulsion. When the surfactant is in presence of salt or when high concentration of surfactant is used, degree of dissociation of polar groups becomes lesser and resulting system may be w/o type.

Property of Oil Phase:

Oil phase also influence curvature by its ability to penetrate & Swell the tail group region of the surfactant monolayer, swelling of tail results into an increased negative curvature to w/o microemulsion.

Packing Ratio:

HLB of surfactant determines the type of microemulsion through its influence on packing and film curvature. The analysis of film curvature for surfactant association`s leading to the formation of microemulsion.

Temperature:

Temperature is extremely important in determining the effective head group size of nonionic surfactants. At low temperature, they are hydrophilic and form normal o/w system. At higher temperature, they are lipophilic and form w/o systems. At an intermediate temperature, microemulsion coexists with excess water and oil phases and forms bicontinuous structure.

Evaluation parameters of microemulsion system [22, 23]

1. Physical appearance:

For physical appearance microemulsion can be inspect visually for homogeneity, fluidity and optical clarity.

2. Scattering techniques:

Scattering techniques such as small angle neutron scattering, small angle X-ray scattering and light scattering have found applications in studies of microemulsion structure, particularly in case of dilute monodisperese spheres, when polydisperse or concentrated systems such as those frequently seen in microemulsions.

3. Limpidity Test (Percent Transmittance):

The limpidity of the microemulsion can be measured spectrophotometrically using spectrophotometer.

4. Drug stability:

The optimized microemulsion was kept under cold condition (4-8°C), room temperature and at elevated temperature (50 ± 2 °C). After every 2 months the microemulsion can be analyzed for phase separation, % transmittance, globule size and % assay.

5. Globule size and zeta potential measurements:

The globule size and zeta potential of the microemulsion can be determined by dynamic light scattering, using a Zetasizer.

6. Assessment of the rheological properties (viscosity measurement):

The rheological properties play an important role in stability. It can be determined by Brookfield digital viscometer. Change in the rheological characteristics help in determining the microemulsion region and its separation from other region. Bicontinuous microemulsion are dynamic structures with continuous fluctuations occurring between the bicontinuous structure, swollen reverse micelle, and swollen micelles.

7. Electrical Conductivity:

The electrical conductivity of microemulsions was measured with a conductivity meter equipped with inbuilt magnetic stirrer. This was done by using conductivity cell consisting of two platinum plates separated by desired distance and having liquid between the platinum plate acting as a conductor.

8. Drug solubility:

Drug was added in excess to the optimized microemulsion formulation as well as each individual ingredient of the formulation. After continuous stirring for 24 h at room temperature, samples were withdrawn and centrifuged at 6000 rpm for 10 min. The amount of soluble drug in the optimized formulation as well as each individual ingredient of the formulation was calculated by subtracting the drug present in the sediment from the total amount of drug added. The solubility of drug in microemulsion was compared with respect to its individual ingredients.

9. Phase behavior studies:

Visual observation, phase contrast microscopy and freeze fracture transmission, electron microscopy can be used differentiate microemulsions from liquid crystals and coarse emulsions. Clear isotropic one phase system are identified as microemulsions where as opaque system showing bifringence when viewed by crosploarized light microscopy may be taken as liquid crystalline system.

10. Freeze thawing method:

Freeze thawing was employed to evaluate the stability of formulations. The formulations were subjected to 3 to 4 freeze-thaw cycles, which included freezing at – 4°C for 24 hours followed by thawing at 40°C for 24 hours. Centrifugation was performed at 3000 rpm for 5 minutes. The formulations were then observed for phase separation. Only formulations that were stable to phase separation were selected for further studies.

11. Measurement of Ph:

The pH values of Microemulsions were determined using digital pH meter standardized using pH 4 and 7 buffers before use.

12. In-vitro drug release:

The diffusion study can be carried out on a modified Franz diffusion cell, within volume of 20 mL. The receptor compartment was filled with of buffer. The donor compartment was fixed with cellophane membrane, containing the microemulsion formulation and the plain drug solution, separately. At predetermined time intervals samples were withdrawn from the receptor compartment and analyzed for drug content, using a UV spectrophotometer at specific wavelength.

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 were subjected to droplet size distribution analysis. Effect of surfactant and their concentration on size of droplet is also to be studied.

Application of microemulsion system [24, 25]

1. Microemulsion in pharmaceuticals:

Parenteral administration: Parenteral administration (especially via the intravenous route) of drugs with limited solubility is a major problem in the pharmaceutical industry because of the 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.

Oral administration: Oral administration of microemulsion formulations offer several benefits over conventional oral formulation including increased absorption, improved clinical potency, and decreased drug toxicity. Therefore, microemulsion has been reported to be an ideal delivery of drugs such as steroids, hormones, diuretic and antibiotics.

Pharmaceutical drugs of peptides and proteins are highly potent and specific in their physiological functions. However, most are difficult to administer orally. With on oral bioavailability in conventional (i.e. non-microemulsion based) formulation of less than 10%, they are usually not therapeutically active by oral administration. Because of their low oral bioavailability, most protein drugs are only available as parenteral formulations. However, peptide drugs have an extremely short biological half life when administered by parenteral route, so require multiple dosing.

Topical administration: Topical administration of drugs can have advantages over other methods for several reasons, one of which is the avoidance of hepatic first pass metabolism of the drug and related toxicity effects. Another is the direct delivery and targetability of the drug to the affected area of the skin or eyes.

Ocular and pulmonary delivery: Ocular and pulmonary delivery for the treatment of eye diseases, drugs are essentially delivered topically. O/W microemulsions have been investigated for ocular administration, to dissolve poorly soluble drugs, to increase absorption and to attain prolong release profile.

For instance microemulsions containing pilocarpine were formulated using lecithin, propylene glycol and PEG 200 as co-surfactant and iso-propyl myristate (IPM) as the oil phase. The formulations were of low viscosity with a refractive index lending to ophthalmologic applications.

2. Microemulsions in biotechnology:

Many enzymatic and biocatalytic reactions are conducted in pure organic or aqua-organic media. Biphasic media are also used for these types of reactions. The use of a pure polar media causes the denaturation of biocatalysts. The use of water-proof media is relatively advantageous. Enzymes in low water content display and have:

1 Increased solubility in non-polar reactants.

2 Possibility of shifting thermodynamic equilibria in favour of condensations.

3 Improvement of thermal stability of the enzymes, enabling reactions to be carried out at higher temperatures.

Many enzymes, including lipases, esterases, dehydrogenases and oxidases often function in the cells in microenvironments that are hydrophobic in nature. In biological systems many enzymes operate at the interface between hydrophobic and hydrophilic domains and these usually interfaces are stabilized by polar lipids and other natural amphiphiles. Enzymatic catalysis in microemulsions has been used for a variety of reactions, such as synthesis of esters, peptides and sugar acetals transesterification; various hydrolysis reactions and steroid transformation. The most widely used class of enzymes in microemulsion-based reactions is of lipases.

3. Solubilization of drug in microemulsion:

Microemulsion possesses interesting physicochemical properties, i.e. transparency, low viscosity, thermodynamic stability, high solubilization power. Because of these specific properties of microemulsion can be useful as a drug delivery system. Different categories of drugs can be solubilized in microemulsion systems for their better therapeutic efficacy.

4. Microemulsions as coatings and textile finishing:

The coating application area is a very promising and rapidly-growing field of microemulsion technology, because the microemulsified resins overcome many of the shortcomings of the more traditional water-based systems without creating the health and pollution problems and flammability hazards of the solvent-based coatings. Due to their stability and small droplet size, microemulsions are ideal, where stability and homogeneity of the finished product is desired. Paint formulations using microemulsions have shown higher scrub resistance, better colour intensity and more stain resistance than those prepared by emulsions.

In principle, three different possibilities of using microemulsions exist for coating applications: (1) for producing microdispersions by using microemulsified monomers, (2) for transferring non-water-soluble polymers into water, and (3) for obtaining specific effects by polymerization in w/o system. An example of such a system is acrylate lattices stabilized by isothiouronium groups, which have been successfully polymerized to yield particle sizes of 0.08mm. The microemulsions of the vinyl resins can be produced by converting them to ionomers in the presence of carefully selected solvent and co-solvent systems. Average particle sizes of about 0.02–0.14mm are formed depending on the system.

5. A microemulsion as fuels:

A microemulsion-based fuel in the presence of water is one of the advantages of stable microemulsion and they are successfully used to reduce soot formation. When the water is vaporized during the combustion, this will lower the heat released and the combustion temperature. As a direct consequence, the emission rate of gases like nitrogen oxides (NOx) and carbon monoxide (CO) will decrease.

The presence of water is also supposed to cause improved fuel atomization, minimization of particulate emission and sooting, and improved fuel economy in terms of price and miles/volume of the fuel. Another interesting feature of microemulsion-based fuel is their capacity to increase the octane number of gasoline and the corresponding octane number for diesel oils. Octane number improvers include formamide, glycols, urea, etc. In diesel fuels, many problems are overcome due to the high combustion temperatures (160–325°C). It is normal that diesel microemulsions contain watersoluble cetane number improvers.

6. Microemulsions as lubricants, cutting oils and corrosion inhibitors:

Microemulsions or reverse micellar solutions are in use as lubricants, cutting oils and corrosion inhibitors for several decades. The presence of surfactant in microemulsion causes corrosion inhibition and the increased water content compared to pure oil leads to higher heat capacity. On one hand the corrosive agents, because of solubilization in microemulsion cannot react with the metal surface and on the other, the metal surface is protected by the adsorbed hydrophobic surfactant film. However, solubilization is selective, and in some cases, other mechanisms might play a role in corrosion prevention. In microemulsions, water with much higher thermal conductivity, imparts higher heat capacity to the system. Such formulations can be used in cutting oil; the oil lubricates the cutting surface, and the water helps to remove the frictional heat generated during the cutting process.

7. Microemulsions in cosmetics:

In many cosmetic applications such as skin care products, emulsions are widely used with water as the continuous phase. It is believed that microemulsion formulation will result in a faster uptake into the skin. Cost, safety (as many surfactants are irritating to the skin when used in high concentrations), appropriate selection of ingredients (i.e. surfactants, cosurfactants, oils) are key factors in the formulation of microemulsions.

Unique microemulsions as hair care products have been prepared. They contain an amino-functional polyorganosiloxane (a nonionic surfactant) and an acid and/or a metal salt. Solubilization of fragrance and flavored oils can be achieved in microemulsions. Cosmetic microemulsions (transparent and translucent) of silicone oils, produced by emulsion polymerization have been reported. They are, however, not thermodynamically stable products because of low solubility of silicone oil in the surfactants. Ultra fine emulsions prepared by condensation method have some advantages in cosmetic and medical products, as they have excellent stability and safety and their droplet size can be readily controlled. Ultrafine emulsions can be regarded as thermodynamically unstable microemulsions, as they are O/W emulsions with droplet size similar to microemulsion. Cosmetic formulations for skin care products using commercial nonionic surfactants and oils usually used in cosmetics are also investigated.

8. Microemulsions in food:

Certain foods contain natural microemulsions. Microemulsions as a functional state of lipids have been, therefore, used in the preparation of foods. Microemulsions form in the intestine during the digestion and absorption of fat. The possibility of producing microemulsion on purpose and using them as tools in food production is, however, a neglected field in food technology. Excellent component solubilization, enriched reaction efficiency and extraction techniques have considerable potential in the area of food technology. An important application of microemulsion is to provide improved antioxidation effectiveness because of the possibility of a synergistic effect between hydrophilic and lipophilic antioxidants. It is known that soybean oil is effectively protected when contained within an L2- phase produced by the addition of monoglycerides (sunflower oil monoglycerides) to water. An approximately 1:5 ratio of monoglycerides to triglycerides is needed to get enough water into the L2-phase (about 5 wt %). In such a system, 200 ppm of tocopherol in the oil and 5% ascorbic acid in the reverse micelles give a dramatic antioxidant effect compared to conventional methods of dissolving or dispersing antioxidants in oils. In fish oils, the same microemulsion-based method to achieve an antioxidant protective effect has also been used. Glycerol has been used instead of water for further improvement of the protectivity.

CONCLUSION:

Microemulsions are an attractive technology platform for the pharmaceutical formulators as it has excellent solubilization properties, transparency and the relatively simple formulation process. There is still a considerable amount of fundamental work characterizing the physico-chemical behaviors of microemulsions that need to be performed before they can live to their potential as multipurpose drug delivery vehicle. Although the number of microemulsions for cosmetic application of highly biocompatible for transdermal delivery system.

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