Optimization of the coating formulation of loxoprofen sodium sustained release pellets by central composite design-response surface methodology / 中国药科大学学报

ABSTRACT

The aim of the study was to optimize the coating formulation of sustained release pellets of loxoprofen sodium by the central composite design-response surface methodology(RSM plus CCD).In the formulation design using RSM plus CCD,independent variables were the ratio of HPMC to EC(X_1) in the sustained coating formulation and polymer load(weight gain,X_2) were selected as in dependent variables,and in vitro accumulated releases from the pellets at 1,4,and 8 h were dependent variables.Multilinear,two and three order quadratic models were used to estimate the relationship between the dependent and the independent variables,and to delineate RSM and overlay contour plots in order to select the optimal formulations in compliance to the hypothesized in vitro releases (%) at 1,4,and 8 h.The results showed that the relationship between dependent and independent variables was best fitted to three-order quadratic equation.The regression equation generated for the hypothesized in vitro cumulative releases(%) at 1,4,and 8 h were Q_(1h) =227.699 2-30.785 9X_1-43.395 4X_2 + 0.917 4X_1~2 +1.820 3X_2~2 +6.803 9X_1X_2-0.131 5X_1~2X_2-0.268 2X_1X_2~2,Q_(4h) =408.254 0-47.427 8X_1-75.229 2X_2 +3.304 0X_2~2 +12.357 3X_1X_2-0.111 8X_1~2X_2-0.5425X_1X_2~2,Q_(8h) =303.539 0-30.417 6X_1-45.114 0X_2 +2.064 4X_2~2 +6.865 0X_1X_2-0.3341X_1X_2~2,respectively.In the optimized coating formulation,the ratio of HPMC to EC was 4.0% and the polymer load 9.0%.Bias between observed and predicted values in vitro accumulated releases were negligible,indicating the high predictability of the selected models.Therefore,RSM plus CCD is applicable in the optimization of the coating formulation of loxoprofen sodium sustained-release pellets.