A NOVEL APPROACH FOR FORMULATION AND EVALUATION OF ANTICONVULSANT BI LAYERED TABLETS

Divalproex sodium is considered as the most important antiepileptic drug and widely used for treatment of epilepsy and bi-polar disorders and prophylaxis of migraine. The present work has been done to formulate bi-layered tablet of Divalproex sodium containing immediate release layer and sustained  release layer. The FTIR study revealed that there was no interaction between drug and polymer and combination can be safely prepared. Both layers were prepared by wet granulation technique as poor flow property exhibited by pure drug. The immediate release layer was formulated by using sodium starch glycolate, croscarmellose sodium as superdisintegrants and  evaluated  for  physical  parameters,  disintegration  time  and  in  vitro  drug  release.  The optimized immediate release layer (IF6) with highest in vitro release of 98.11 was selected for bi-layered tablet formulation. HPMC K4M and HPMC K100M polymer used to retard the drug release from sustained release layer in different proportion and combination and evaluated for physical parameter along with in vitro drug release studies.. The optimized sustained release layer (SF8) which extends the Divalproex sodium release more than 18 hrs was selected. In vitro drug release studies were performed using USP type II apparatus (paddle method) in 900 ml of phosphate buffer pH 6.8 at 100 rpm. Finally Bi-layered tablets were prepared by double compression of selected sustained release layer and immediate release layer of Divalproex sodium. The tablets were evaluated for hardness, thickness, weight variation, friability, drug content uniformity and in vitro drug release. All the physical parameters were in acceptable limit of pharmacopeial specification. The stability studies, shown the bi-layer tablet was stable at 40°C/ 75% RH for a period of 3 months.

Keywords: Bi-layered tablet, epilepsy, wet granulation, Divalproex sodium, immediate release, sustained release