Pharma gyan Pandit

Microemulsion

Microemulsions are thermodynamically stable, optically transparent, isotropic dispersions of aqueous and hydrocarbon liquids stabilized by an interfacial film of surfactant molecules.

Microemulsions are monodispersed spherical droplets (droplet size below 0.15 µm)  of water in oil, oil in water or may even be bicontinuous, depending on the nature of the continuous phase. The HLB value of the surfactant is an essential criteria to be considered in the formulation of emulsions.

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:

a)     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.

b)     They reduce the mismatch with solvent through a specific kind of aggregation process known as micellization.

History

The Microemulsion concept was introduced as early as 1940s by Hoar and Schulman who generated a clear single-phase mixture by titrating a milky emulsion with hexanol. Schulman and co-workers (1959) subsequently coined the term microemulsion.

Synonyms: Transparent emulsion, Swollen micelle, Micellar solution, Solubilized oil

In recent years, micro emulsion drug delivery system, is a  promising delivery systems which allow  sustained or controlled drug release for percutaneous, peroral,  topical, transdermal, ocular and parenteral administration of  medicaments.

Properties

Spontaneous formation, Ease of manufacturing and scale-up, better alternative drug carrier, Thermodynamic stability, Improved drug solubilization of hydrophobic drugs and bioavailabilty & Increased absorption.

Advantages

1)     Thermodynamically stable system

2)     They can solubilize hydrophilic and lipophilic drugs including drugs that are insoluble relatively insoluble in any of them.

3)     The small size of droplets in microemulsions e.g. below <0.15µ, yields very large interfacial area.

4)     Microemulsion have low viscosity compared to other emulsion.

5)     It increases the bioavailability of drug molecule.

6)     They may become unstable at low or high temperature but when the temperature returns to the stability range, the microemulsion reforms.

7)     Decreased pain sensation at injected site.

Disadvantages

1)     A large concentration of surfactant and co-surfactant necessary for stabilizing the nanodroplets.

2)     The surfactant must be non-toxic for use in pharmaceutical applications.

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

Type of Microemulsion System

Constituents of Microemulsion

Oil phase :- Isopropyl Myristate , Oleic acid , Olive oil, Mineral oil, Medium  chain triglyceride, Soybean oil , Captex 355, Isopropyl palmitate , Sunflower Oil, Safflower Oil .

 Surfactants :- Tween 80, Tween 40, Labrafil M1944CS, Polyoxyethylene-35-ricinoleate,  Brij 58, Span 80, Cremophor EL Labrasol , Cremophor RH,Lecithin .

 Cosurfactant/Stabilizer :- Propylene glycol, Cremphor RH 40, Ethylene glycol, Ethanol, 1-butanol, Isopropyl alcohol,  PEG 600, Glycerol, PEG 400, Sodium Oleate .

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.

Role of surfactant

1)     The surfactant used to stabilize the micro emulsion  system are:

–     Non ionic

–     Zwitter ion

–     Cationic

–     Anionic

2)     The use of hydrophilic surfactant oil produces swollen type of oil-in-water micro emulsion.

3)     The use of lipophilic surfactant produces water swollen type of water-in oil micro emulsion.

4)     The combination of ionic and nonionic surfactant , can be very effective at the microemulsion region.

Role of temperature

The effect of change of temperature at the maximum solubility is very high as the rate of solubilization increases. If temperature insensitive three phase system are produced, micro emulsion are stable against temperature change.

Phase Behaviour

The phase behaviour of simple microemulsion system can be studied by the aid of ternary phase diagram (at fixed pressure and temperature) in which each corner of the diagram represents 100% concentration of that component. 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. The number of different phases present for a particular mixture can be visually assessed.  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. At a limiting water content, the isotropic clear region changes to a turbid, birefringent one. Upon further dilution with water, a liquid crystalline region may be formed in which the water is sandwiched between surfactant double layers. 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)

Spontaneous Emulsification Process

This procedure comprises the following steps:

1)     Dissolving the oil phase containing phospholipid in the alcoholic solution;

2)     Optionally dissolving the drug into the oily alcoholic phase and

3)     Mixing the product of step (2) with an aqueous preparation of surfactant. forming an oil-in-water emulsion. And

4)     Removing (atleast most of) co-solvent which is present.

The emulsions exhibited a mean droplet size in the range 200-300 nm. The results indicated that emulsions prepared by this method are very stable. hey can also be sterilized by heat sterilization or by filtration.

SolEmuls Technology

1)     Drug-loaded emulsions are produced either by adding the powdered drug to the emulsion by stirring or alternatively by preparing a finely wet-milled drug suspension which was mixed with the emulsions by gentle stirring.

2)     The obtained dispersions containing oil droplets and drug crystals are then subjected to a high pressure homogenization process.

3)     Production is performed typically at 45^◦C applying 1500 bar and 1–20 homogenization cycles.