Abstract: OBJECTIVE To optimize the formulation of a premixed film coating powders by the central composite design-response surface methodology(RSM plus CCD). METHODS In the formulation design, independent variables were the amount of the film coating powders HPMC, PVA and plasticizer PEG, and viscosity of the premixed film coating solution, permerbility and tensile stress of the film coating as indexes were dependent variables. Mathematic models were used to estimate the relationship between them, and to delineate RSM and overlay contour plots in order to select the optimal formulation with the application of hypothesized indexes. RESULTS The quantitative relationships between dependent and independent variables were characterized. The best-fitted mathematic models were selected. Bias between observed and predicted values of the film coating indexes were negligible indicating the high predictability of the fit models. CONCLUSION The multi-objective simultaneous optimization of the formulation of a film coating powders could be achieved by RSM plus CCD. The models developed in this study are proved to be predictable and feasible.