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 treatment of epilepsy may induce many adverse side effects on various systems. To minimize unwanted toxic effects by kinetic control of drug release, 1 was physically entrapped into white beeswax microspheres using the meltable dispersion process utilizing wetting agents. Solid, discrete, reproducible free flowing microspheres were obtained converting the liquid drug droplets into solid material. The average drug content was 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 the amount of incorporated drug and to characterize the in vitro release profile. The matematical approach to drug release using standard equations indicated that the first order equationis was the most appropriate one for describing the initial drug release profile; after about the 50-60% of drug was discharged numerical data fit well with the root of time equation. The drug removal from microspheres was compared with that obtained from a commercially available enteric coated oral formulation of 1 (Depakin(R)). The drug release performance was greatly affected by the microsphere formation which allows absorption only in the intestinal tract.