Studies in preparation and evaluation of pH-independent sustained-release matrix tablets of verapamil HCl using directly compressible Eudragits

The objective of the present study was to investigate the impact of formulation factors on the properties of a 12h modified-release formulation of verapamil HCl. A 2(3) full factorial design was employed to investigate the influence of amount of Eudragit RS PO/RL PO (X-1, a matrixing agent), HPMC K4M (X-2, an auxiliary matrixing agent cum binder) and PEG 4000 (X-3, channelling agent cum plasticizer). The tablets were prepared by direct compression and they were evaluated for in vitro dissolution studies in 0.1 N HCl. The time required for 90% of the drug release (t(90)) and similarity factor (f(2)) were used as responses for the selection of most appropriate batches. Swelling and fluid penetration studies were carried out in 0.1 N HCl. Time required for 90% of the drug release (t(90)) was calculated by using an appropriate kinetic model for each batch. An ideal drug release profile (i.e., 25% in the first hour and a constant drug release thereafter) was considered as a reference release profile for calculation of f(2). Multiple regression analysis was adopted to evolve refined models for t(90). The required release pattern was shown by batches containing a low level of Eudragit RS PO/RL PO (30% w/w), low level of HPMC K4M (10% w/w), and high level of PEG 4000 (15% w/w). Response surface plots are shown for t(90). These formulations showed slower drug release in alkaline medium (pH 7.2). Succinic acid and KH2PO4 were incorporated in the matrix in order to obtain pH-independent drug release. Swelling of tablets and fluid penetration in the matrix were found to be influenced by the selected independent variables. This study demonstrates that the desired drug release pattern can be obtained by adopting a systematic formulation approach.