Use of Eudragit RS PO, HPMC K100M, Ethyl Cellulose, and Their Combination for Controlling Nicorandil Release from the Bilayer Tablets with Atorvastatin as an Immediate-Release Layer

Abstract

To develop a bilayer tablet containing sustained-release (SR) nicorandil and immediate-release (IR) atorvastatin components in separate layers for the effective treatment of angina accompanied by hyperlipidemia with less dosing frequency and improved patient compliance. Sustained-release nicorandil layer was formulated using HPMC K100M with or without Eudragit RS PO and Ethyl Cellulose 10FP. An immediate-release atorvastatin layer was developed using crospovidone and sodium carbonate. The formulations were optimized using a central composite design with the help of Design Expert software. The bilayer tablets were manufactured using a double-compression technique. Dissolution test study was conducted using three different media (pH 1.2, 4.5, and pH 6.8 buffers). Dissolution profiles were analyzed through model-dependent and model-independent methods using DDSolver, an Excel-based add-in program. Selected formulations were subjected to accelerated stability study according to ICH guidelines. The bilayer tablets were successfully developed with desired quality attributes. Nicorandil release kinetics followed anomalous diffusion, and in vitro release profile was best expressed through the Higuchi equation, while atorvastatin release exhibited Weibull kinetics. The shelf-life of optimized formulations was found to be about 13 months. The combination of ethyl cellulose and HPMC K100M successfully controlled the release of nicorandil from the bilayer tablet containing immediate-release atorvastatin. The formulation can be subjected to pharmacokinetic studies and clinical trials in the future for better management of cardiovascular diseases and enhancing patient compliance.