Formulation development of multilayer sustained release tablets of sodium valproate combined with valproic acid

Abstract

The purpose of this study was to formulate and evaluate the effect of different polymers on drug release from sodium valproate matrix tablet and develop multilayer sustained release tablets that composed of sodium valproate only and combined with valproic acid. They were prepared by direct compression method using various amount of colloidal silicon dioxide (2.5-5%w/w) as an adsorbent, talcum, dibasic calcium phosphate as excipients. The polymers used were:, ethylcellulose, HPMC E4M, HPMC K15M, xanthan gum, carrageenan, sodium alginate, Kollidon® SR and Eudragit® RSPO (5-20%w/w). Among the eight polymers, HPMC K15M led to more retardation of drug release. The concentration of HPMC K15M employed in tablet formulations affected drug release from matrix tablets. Then, HPMC K15M was also used as a rate controlling polymer in the outer layers. The drug released from multilayer formulations were sustained for 24 hours. The formulation that composed of only sodium valproate released drug from tablet faster than that composed of sodium valproate combined with valproic acid. Drug release profiles of multilayer sustained release tablets of sodium valproate and those of sodium valproate combined with valproic acid best fit to zero order release model, while the mechanism of drug release was non-fickian diffusion.