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 phenyt oin (1) was developed and evaluated in vitro. The preparation consists of gastroresistant microparticulate drug delivery system formulated w ith oleaginous material (lipospheres) to minimize unwanted effects of 1 on gastric apparatus. The drug was dispersed in a spherical micromat rix 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 dilaurat e and stearyl alcohol (ratio 3:17). The lipospheres were obtained by a technique involving melting anal dispersion of drug-containing oleagi nous material in aqueous medium. The oily droplets of the resulting em ulsion 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 vario us particle sizes and to characterize the in vitro release profile. Th e average drug content was 23.8% w/w. Drug encapsulation efficiency wa s about 93.6% and the yield of production ranged from 94 to 98%. The d rug discharge pattern from the microparticulate system in the intestin al environment was evaluated. Kinetic results were analyzed to disting uish between various release models. The matrix diffusion-controlled e quation was the most appropriate one in describing drug release.