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), h ave been characterized. The particles were prepared by precipitation o f CA in the dispersed phase of an o/w emulsion stabilized by two diffe rent emulsifier systems i.e., (a) a mixture of lecithin and sodium gly cocholate and (b) a polyoxyethylene sorbitan fatty acid ester. The par ticle size has been determined by photon correlation spectroscopy (PCS ) and transmission electron microscopy (TEM). The average particle siz e, by number, was determined by PCS to be 21-144 nm depending on the e mulsifier system used in the particle preparation. The smallest mean p article 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 b e amorphous, exhibiting neither microporosity in the particles nor agg regation between the particles. The transition temperature of choleste ryl acetate in the particles prepared with the blend of lecithin and s odium glycocholate has been determined by differential scanning calori metry (DSC). The DSC measurements indicate that the melting point at 1 05-degrees-C of the cholesteryl acetate particles prepared with lecith in/sodium glycocholate is lower than that of the pure macroscopic chol esteryl acetate crystals which is 116-degrees-C. The irreversible tran sition of cholesteryl acetate at about 80-degrees-C was not observed i n the particle form of cholesteryl acetate prepared with the emulsifie r blend of phosphatidyl-choline and sodium glycocholate. The suspensio ns 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.