Optimization of pulsatile-controlled release tablets of metoprolol fumarate by central composite design-response surface methodology

Purpose To determine the optimal formulation of explosion pulsatile-controlled release tablets of metoprolol fumarate(MF).Methods The formulation was optimized using central composite design and response surface metholodgy.The effects of five independence variables,HPMC(mg),Eudragit L100(mg),PEG6000(mg),disintegrants(mg),and thickness of the coating films(%) were evaluated.Response variables selected in the research were percent of accumulated release(Q) of 5,7,12,16 h.The data were transformed into desirabilities.Overall desirability was calculated from the geometric mean of the four desirabilities of each formulation.The second-order polynomial and linear equations were fitted to the data of overall desirabilities,and the resulting equation was used to produce 3-D response surface graphs,through which the optimal formulation was predicted.Results The second-order polynomial equation was superior to the linear one,and regression coefficient of the nonlinear estimation was higher than 0.929 2.The pulsatile-controlled release tablets prepared according to the optimal experimental conditions resulted in an overall desirability of 0.834 0.The bias between observed and predicted values of the overall disrability of the optimal formulation was-4.35%.Conclusion Central composite design-response surface methodology is successfully used to optimize the formulation of MF pulsatile-controlled release tablets