PREPARATION OF WHITE BEESWAX MICROSPHERES LOADED WITH VALPROIC ACID AND KINETIC-STUDY OF DRUG-RELEASE

The well known antiepileptic valproic acid (1) due to the long treatme nt of epilepsy may induce many adverse side effects on various systems . To minimize unwanted toxic effects by kinetic control of drug releas e, 1 was physically entrapped into white beeswax microspheres using th e meltable dispersion process utilizing wetting agents. Solid, discret e, reproducible free flowing microspheres were obtained converting the liquid drug droplets into solid material. The average drug content wa s 17% w/w. More than 95% of the isolated microspheres were of particle size range 200-425 mu m. The microspheres were analyzed to quantify t he amount of incorporated drug and to characterize the in vitro releas e profile. The matematical approach to drug release using standard equ ations indicated that the first order equationis was the most appropri ate one for describing the initial drug release profile; after about t he 50-60% of drug was discharged numerical data fit well with the root of time equation. The drug removal from microspheres was compared wit h that obtained from a commercially available enteric coated oral form ulation of 1 (Depakin(R)). The drug release performance was greatly af fected by the microsphere formation which allows absorption only in th e intestinal tract.