Optimization of push-pull osmotic pump controlled release tablets containing felodipine by central composite design-response surface methodology

OBJECTIVE To optimize the formulation of push-pull osmotic pump controlled release tablets containing felodipine by the central composite design-response surface methodology.METHODS In the formulation design,the effects of five independence variables,the amount of NaCl、PEO、HPMC K4M,the ratio of cellulose to PEG 4000,tablet weight gain for membrane coating,were evaluated.Response variables selected in the research were in vitro cumulative releases at 2,8,12 and 16 h.The data were transformed in desirabilities.Overall desirability was calculated from the geometric mean of the four desirabilities of each formulation.Multilinear and quadratic models were used to estimate the relationship between the dependent and the independent variables,and to delineate RSM and contour plots in order to select the optimal formulations.RESULTS The optimized area predicted by quadratic model had better prediction capability than that by multilinear model.In vitro release test indicated that there existed high approximation between the observed and estimated values.CONCLUSION The multi-objective simultaneous optimization of push-pull osmotic pump controlled release tablets containing felodipine could be achieved by the central composite design and response surface methodology.