Optimization and Validation of Modulated Release Formulation 0f Ranitidine HCl by Response Surface Methodology

The objective of the present study was, 1) to systematically device a model of factors that would yield an optimized sustained release dosage form of model drug (Ranitidine HCl), 2) to validate the models using R2 values,3) to optimize the formulation by response surface methodology (RSM); A three – factor, three – level Box – Behnken design was used for the optimization procedure, with the amounts of HPMC-K100M (X1), PVPk-90 (X2), Compression Force (X3) as independent variables. Three dependent variables were considered: percentage of drug release at 1hr, 12hrs, T50%. The regression equation obtainedY2 = 92.41 + 3.18X1+ 2.05 X2 + 2.14X3 + 2.41X1X2 + 0.24 X1X3 + 0.11 X2X3 -3.82X1 2 - 2.59X2 2 -0.46X3 2 explained the main and interaction effects of factors that influenced the drug release. Optimization was performed by maximizing the drug release in 12 hrs and placing constraints on Y1, Y2 and Y3. Validation of optimization by carrying out by performing 8 experimental runs showed high degree of prognostic ability of response surface methodology. The results showed that the optimized formulation provided a dissolution pattern similar to the predicted curve, which indicated that the optimal formulation could be obtained using RSM. A simple high performance liquid chromatography method was developed and the dissolution samples were analysed by this procedure.