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Microemulsion-Based Technique

Gasco and coworkers were the first to develop SLNs based on the dilution of microemulsions. Microemulsions are thermodynamically stable, clear, and isotropic mixtures, usually composed of an oil or lipid, emulsifier and/or coemulsifier, and water. Lipids used to prepare SLNs are solids at room temperature, and hence the microemulsion is prepared at a temperature above the melting point of the lipid. Both the lipid and the aqueous phase containing the emulsifier are mixed in appropriate ratios and stirred so that it will produce a microemulsion. The hot microemulsion is then diluted with cold water (2—8°C) while stirring. The ratio of the hot microemulsion to cold water is usually in the range of 1:25 to 1:50. It has been noted in the literature that a droplet structure is already present in the microemulsion, and therefore no external energy is required to achieve the small particle size. When the microemulsion is diluted by cold water, the lipid droplets solidify as the temperature decreases. The temperature gradient and pH value determine the quality of the product, in addition to the composition of the microemulsion. The major limitation ofthis technique is its sensitivity to minor changes in composition or thermodynamic variables, which can lead to phase transitions. The lack of robustness of the microemulsion technique can lead to high production costs. Moreover, solidification of lipids shifts the system to a thermodynamically unstable state. Due to the dilution of the microemulsion, the concentrations of particle content are below 1%; therefore a large amount of water has to be removed to process the SLNs to a final dosage form. The high concentration of surfactants used may produce toxicity. This necessitates removal of excess surfactants using ultracentrifugation, ultrafiltration, or dialysis.

 
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