Optimization of ambroxol hydrochloride sustained-release tablets formulation by central composite design-response surface methodology

Aim:To optimize the formulation of ambroxol hydrochloride sustained-release tablets by the central composite design-response surface methodology(RSM plus CCD).Methods:In the formulation design using RSM plus CCD,independent variables were the amounts of HPMC and lactose,and percentages of in vitro cumulative releases at 2,8,16 and 24 h were dependent variables.Multilinear and 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 with the application of hypothesized in vitro cumulative releases(%)at 2,8,16 and 24 h.Results:The quantitative relationships between two factors and four evaluation indexes were characterized.The optimized area predicted by multilinear model was found moderately larger than that by quadratic model.In vitro release test of three selected optimal formulations indicated that there existed high approximation between the observed and estimated values.Moreover,multilinear model had better prediction capability than quadratic model did.Conclusion:Multilinear model was preferred in the optimization of formulation due to the statistical confidence and the simplicity in calculation.The multi-objective simultaneous optimization of ambroxol hydrochloride sustained release tablets formulation could be achieved by the central composite design and response surface methodology.