DESIGN AND STATISTICAL OPTIMIZATION OF A BILAYERED TABLET OF METOPROLOL SUCCINATE SUSTAINED RELEASE AND ATORVASTATIN CALCIUM IMMEDIATE RELEASE: ONCE A DAY FORMULATION IN THE MANAGEMENT OF HYPERTENSION

Abstract

 Objective: The current study involves the fabrication of oral bilayer matrix designs of a combination of two drugs, metoprolol succinate and atorvastatin calcium, the optimization of their in vitro release and characterization using the design expert software. Metoprolol succinate, a β1- selective adrenergic receptor blocking agent, is used in the management of hypertension has a half-life of approximately 4–5 h; thus, there is the need to use extended-release formulation for prolonged action. Atorvastatin is a hydroxymethylglutaryl-coenzyme A reductase inhibitor, an antilipidemic, used to lower blood cholesterol. The rationale for this fixed-dose combination is to coadminister two drugs acting by different mechanisms of action together, reduce dosing frequency, and increase patient compliance.

Methods: A 32 factorial design was selected to analyze the effect of critical factors, polymer concentration of Kollidon sustained release (SR), and Eudragit RS and their interaction on the in vitro release of the SR part containing metoprolol succinate. The drug release at 2 h (Q2), 8 h (Q8), and 20 h (Q20) was taken as responses. The blends of both layers were prepared, evaluated for precompression characteristics, and compressed by direct compression. The compressed bilayer tablets were evaluated for their hardness, weight variation, friability, content uniformity, diameter, and in vitro release.

Result and Conclusion: The release profile indicates Higuchi's kinetics. Contour and surface response plots show significant interaction among the formulation variables. Formulation MS06 containing 70 mg Kollidon SR and 10 mg Eurdragit RS was found to be the optimized formulation, controlling the drug release for a 24 h period.