STATISTICAL OPTIMIZATION AND QUALITY BY DESIGN (QBD) APPROACH FOR THE DEVELOPMENT OF METHOCARBAMOL DELAYED-RELEASE TABLETS USING POLYMER BLENDS

Abstract

The present study utilizes the principle of rheological synergism between hydrophilic polymers in development of pharmaceutical formulations, more specifically to develop and evaluate delayed release matrix tablet using polymer blends. Methocarbamol is an FDA approved centrally acting skeletal muscle relaxant. It works by calming overactive nerves in body, which helps muscles to get relaxed but its mechanism of action is not well defined and its effects are measured mainly by subjective responses. Half-life of Methocarbamol is short so it is necessary to prolong drug action, hence it was decided to develop matrix tablets as desired dosage form. HPMC, SCMC, its blends and marketed Instamodel 41 and 49 polymer blends were used for the study. Further Instamodel 41 was selected and matrix tablets were further coated with Instacoat EEN to protect drug release in upper GIT. Preliminary trial batches were studied for pre and post compression evaluation test. Formulation showed desirable lag time and dissolution profile were further optimized by applying 32 full factorial design to study the effect of extent of coating (% w/w) Instacoat EEN and Instamodel 41 matrix tablet were selected as independent variables X1 and X2 respectively and two responses as lag time and Cumulative % drug release at 18 hours as Y1 and Y2 respectively. Various kinetic models were applied to the all optimized batches. All F1-F9 and optimized solution batch M results complied with IP standards. The regression equation generated for Lag Time = 9.35- 3.76 A + 0.7533B and for % CDR = +93.93 – 0.9717 A – 4.27 B. The drug release data of optimized formulation were close to that predicted by the model. The formulation M with 5.903 %w/w Instacoat EEN and 125 mg w/w Instamodel 41 was found to be optimum. The present study demonstrates that Methocarbamol enteric coated matrix tablet could be successfully released in lower GIT with delayed action.