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(X₁)in the sustained coating formulation and polymer load(weight gain，X₂) were selected as in dependent variables，andin vitroaccumulated 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 hThe 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_{1 h}=227.699 2-30.785 9X₁-43.395 4X₂+0.917 4X ₁²+1.820 3 X₂²+6.803 9X₁X₂-0.131 5X₁²X₂-0.268 2X₁X₂²，Q_{4 h}=408.254 0-47.427 8X₁-75.229 2X₂+3.304 0X₂²+12.357 3X₁X₂-0.111 8X₁²X₂-0.5425X₁X₂²,Q_{8 h}=303.539 0-30.417 6X₁-45.114 0X₂+2.064 4X₂²+6.865 0X₁X₂-0.334 1X₁X₂²，respectively.In the optimized coating formulation，the ratio of HPMC to EC was 40% and the polymer load 90% 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.