Study of Influence of Formulation Variables on Drug Release: Optimization of Sustained Release Matrix Tablets of Metoclopramide HCl Using Central Composite Experimental Design

Metoclopramide Hydrochloride (MCP), has a short half-life. In order to maintain therapeutic levels in blood, it administered in dose of 10-15 mg four times a day. Fluctuation in plasma concentration of drug is commonly observed for drugs that are rapidly absorbed and eliminated when used in long term therapy. This attribute makes metoclopramide a suitable candidate for controlled release delivery. In this work HPMC K4M was used as release rate controlling polymer for the development of controlled release tablet formulation. Experimental Design using CCRD was utilized to determine the influence of varying the concentration of different variables such as polymer and diluents on the release behavior of the drug from matrix tablets and optimization of formulation. Different SR formulation prepared were designed and optimized with the help of software Design Expert® version 10. Using Central Composite Rotatable Design (CCRD), fifteen formulations were selected and prepared using HPMC K4M, Avicel PH-102 and Lactose DC as variables. All the trial formulations were evaluated using different pharmacotechnical tests including hardness, friability, disintegration, dissolution. Online Dissolution apparatus type II and 900 ml different dissolution media in the pH range 1-6.8 and distilled water for dissolution. The drug release was studied by applying the dissolution models by DDSolver® software. Hixson-Crowell model was best fit to the F13 SR formulation. The CCRD experimental design was successfully used in optimization of sustained release Metoclopramide HCl formulation