Entrapment of phenytoin into microspheres of oleaginous materials: Process development and in vitro evaluation of drug release

A novel multiparticulate preparation of the antiepileptic agent phenytoin (1) was developed and evaluated in vitro. The preparation consists of gastroresistant microparticulate drug delivery system formulated with oleaginous material (lipospheres) to minimize unwanted effects of 1 on gastric apparatus. The drug was dispersed in a spherical micromatrix consisting of a mixture of stearyl alcohol and glycerol esters of various fatty acids. The best mixture to obtain discrete, reproducible, free-flowing lipospheres consisted of glyceryl monostearate dilaurate and stearyl alcohol (ratio 3:17). The lipospheres were obtained by a technique involving melting anal dispersion of drug-containing oleaginous material in aqueous medium. The oily droplets of the resulting emulsion after cooling under rapid stirring were transformed into solid. About 99% of the lipospheres were of particle size range 100-800 mu m. The lipospheres were analyzed to determine the drug content in various particle sizes and to characterize the in vitro release profile. The average drug content was 23.8% w/w. Drug encapsulation efficiency was about 93.6% and the yield of production ranged from 94 to 98%. The drug discharge pattern from the microparticulate system in the intestinal environment was evaluated. Kinetic results were analyzed to distinguish between various release models. The matrix diffusion-controlled equation was the most appropriate one in describing drug release.