Abstract

The main objective of this investigation was to formulate controlled release dosage form by using citric acid cross linked cellulose based hydrogel. Hydrogels were prepared by cross liking the polymer HPMC-K4M by using suitable cross linking agent, citric acid. Due to cross linking reaction hydrogel gave good swelling as well as controlled release property to metoprolol succinate hydrogels. In this study 3 2 full factorial design, which was augmented for 2 central points was used by using Design-Expert 8.0.7.1. It gave 11 runs. In this design the concentration of citric acid (X1) and reaction time (X2) were selected as independent variables, while as drug content, swelling index and t 75 of % cumulative drug release were selected as dependent variables. From the results it can be concluded that the effect of citric acid concentration on drug content and t 75 of % CDR was nonsignificant. But the effect of citric acid concentration on swelling index was much significant, means as citric acid concentration increased; there was decrease in swelling index of hydrogel. Again effect of reaction time on drug content as well as on t 75 of % CDR was much significant, means as reaction time increased; there was increase in drug content as well as t 75 of %CDR of hydrogel. But the effect of reaction time on swelling index was nonsignificant. On the basis of all responses obtained, drug content, swelling index and t 75 of % CDR of run R1 are best. Drug content, swelling index and t 75 of % CDR of this run are 99.5%, 276.64% and 207.6 min. respectively. So optimized formulation was run R1, which gave the best in vitro release up to 94.24% in 360 min (6hrs).IR and DSC study shows no evidence on interaction between drug, polymers and other excipient. The in vitro data were fitted to different kinetic models.

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