PREPARATION AND EVALUATION OF CONTROLLED-RELEASE SODIUM VALPROATE / VALPROIC ACID (VALDISOVAL) TABLETS

Abstract

Valdisoval (VL) is a mixture of sodium valproate (SV) and valproic acid (VA) in a 2:1ratio. Different polymers were used to develop a controlled-release tablet formulation for VLusing either direct compression or wet granulation techniques. Eudragits RSPO and RLPO indifferent concentrations were used as direct compression and rate controlling polymers, whileethyl cellulose (EC), hydroxy propyl methyl cellulose (HPMC) and hydroxy ethyl cellulose(HEC) were used as release retardants in the wet granulation matrix formulations. Tabletsprepared showed good physical properties; e.g. hardness, friability, weight variations, usingdifferent polymers by direct compression and wet granulation techniques. The release profile ofSV from the compressed tablets was studied using the USP dissolution apparatus II at 100 rpmin either distilled water for 8 hours or in 0.1 N HCl for one hour followed by phosphate buffer,pH 6.8 for another 7 hours. Sodium valproate release was found to decrease by increasing theconcentration of Eudragit RSPO in the formula and was less affected by the concentration ofEudragit RLPO.The release of SV from the tablets containing ethyl cellulose as tablet matrixwas affected by the type of the binder in the wet granulation process. This was indicated by thedifference in T50% (time for 50% of the drug to be released). HEC was used as a releaseretardant in a concentration range 10 to 25% w/w. The release of SV from these tablets wasinversely proportional to HEC concentration in the formula.Tablets containing 12.5% w/w ofthis polymer were film coated using Eudragit L100-55.When the release profile of SV from thesetablets was compared to a marketed product (Depakine ChronoR) under the same conditions, analmost identical dissolution pattern was found. Zero order release kinetics was elucidated fromthe dissolution data.