Development of fixed dose combination tablets of aripiprazole plus divalproex sodium and their simultaneous determination using HPLC-UV.

A vast majority of psychiatric patients are effectively treated with combination of drugs to improve efficacy and adherence, but due to limited research and development in fixed dose combination (FDC) in psychiatry, these products are not commonly available. The aim of this study is to prepare cost effective FDC tablets containing aripiprazole and divalproex sodium. Two batches of fixed dose combination tablets, FDC1 and FDC2, were successfully prepared using wet granulation technique. Furthermore, aripiprazole tablets A1 and A2 and divalproex tablets D1 were also formulated as reference to compare the in vitro availability profile. An accurate and simple isocratic HPLC method was established and validated for the simultaneous quantification of aripiprazole and valproic acid in the FDC tablets. A reversed-phase C18 (250 × 4.6 mm) column in isocratic mode was used. The mobile phase consisted of acetonitrile and 0.32% KH2PO4 (60:40, v/v), flow rate was set at 1.0 mL/min and the detection was performed at 210 nm. Average percent recoveries of aripiprazole and valproic acid were 96.0 and 95.5%, respectively, meeting the official requirements. The newly developed FDC product may be used for the better therapeutic outcomes of combined use of aripiprazole and valproic acid, which may improve patient adherence.