Lecithin-Based Microemulsions for Pharmaceutical use - Phase behavior and Solution Structure

Abstract: Microemulsions are thermodynamically stable, transparent solutions of water, oil and amphiphile(s). It is possible to incorporate large amounts of oil in microemulsions, which makes them interesting for use as a drug delivery vehicle for water insoluble drugs. A prerequisite for pharmaceutical use, however, is a low toxicity of the composition. The aim of this thesis has thus been to characterize microemulsion systems based on the pharmaceutically acceptable components lecithin (soybean phosphatidylcholine), medium-chain and long-chain triglycerides and isopropyl myristate (IPM). An analysis was made of the microstructure of these systems and their phase behavior determined. The effect of the addition of hydrophilic amphiphiles (the IPM system) and of two drug compounds, felodipine and BIBP3226 was also analyzed. Felodipine, being practically insoluble in water and slightly soluble in MCT, was found to act as a non-penetrating oil with only a slight influence (decrease) on the curvature of the amphiphilic film. BIBP3226, on the other hand, being practically insoluble in MCT but slightly soluble in the aqueous phase, had an affinity for the lecithin monolayer which significantly increased both the solubility and the spontaneous curvature of the film. At the point of saturation, approximately 60 percent of the drug molecules were located in the film. A microemulsion system suitable for intravenous administration is presented. It is composed of a medium-chain triglyceride as the oil, soybean phosphatidylcholine and polyethylene glycol(660)-12-hydroxystearate as amphiphiles, and polyethylene glycol 400 and ethanol as cosolvents. The microstructure of this microemulsion was found to be of a bicontinuous nature, even at high oil concentrations. When diluted with water, the microemulsion spontaneously formed an oil-in-water emulsion with a mean droplet diameter between 60 and 200 nm depending on the oil content of the microemulsion. It was possible to administer up to 1.5 ml/kg of the microemulsion intravenously to conscious rats without causing any permanent changes in the hemodynamic parameters studied.