PREPARATION OF SUBMICRON DRUG PARTICLES IN LECITHIN-STABILIZED O/W EMULSIONS .2. CHARACTERIZATION OF CHOLESTERYL ACETATE PARTICLES

Submicron particles of a model drug, viz., cholesteryl acetate (CA), have been characterized. The particles were prepared by precipitation of CA in the dispersed phase of an o/w emulsion stabilized by two different emulsifier systems i.e., (a) a mixture of lecithin and sodium glycocholate and (b) a polyoxyethylene sorbitan fatty acid ester. The particle size has been determined by photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM). The average particle size, by number, was determined by PCS to be 21-144 nm depending on the emulsifier system used in the particle preparation. The smallest mean particle size of 21 nm was achieved with a blend of lecithin and sodium glycocholate. According to TEM pictures, the particles have a smooth surface and are spherical, and the majority of the particles seem to be amorphous, exhibiting neither microporosity in the particles nor aggregation between the particles. The transition temperature of cholesteryl acetate in the particles prepared with the blend of lecithin and sodium glycocholate has been determined by differential scanning calorimetry (DSC). The DSC measurements indicate that the melting point at 105-degrees-C of the cholesteryl acetate particles prepared with lecithin/sodium glycocholate is lower than that of the pure macroscopic cholesteryl acetate crystals which is 116-degrees-C. The irreversible transition of cholesteryl acetate at about 80-degrees-C was not observed in the particle form of cholesteryl acetate prepared with the emulsifier blend of phosphatidyl-choline and sodium glycocholate. The suspensions have also been investigated by small angle X-ray scattering (SAXS). The cyclohexane residue in the resulting suspensions was below 25 ppm according to analysis by gas chromatography.