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A mathematical optimization technique was applied to obtain a formulation of indomethacin (IMC)/polyvinylpolypyrrolidone/methyl cellulose solid dispersion with a high dissolution rate and high stability of IMC. Model formulations were prepared according to a composite spherical experimental design based on the simplex method. The dissolution rate and chemical stability of IMC were determined as response variables for deciding an optimum formulation. These response variables were predicted by the second-order polynomial regression model of formulation and process factors. In order to optimize the formulation, regression equations of each response were mathematically structured as a constrained nonlinear optimization problem. The solution was obtained by application of the sequential unconstrained minimization technique. Experimental results obtained for the optimum formulation agreed well with the predictions.