FORMULATION & OPTIMIZATION OF SUSTAINED RELEASE MATRIX TABLETS OF SIMVASTATIN USING RESPONSE SURFACE METHODOLOGY

摘要

The aim of the work is to formulate sustained release matrix tablets of simvastatin and to optimize them using Response Surface Methodology. The tablets were prepared by direct compression method and evaluated as per pharmacopoeia methodology. A central composite design for 2 factors at 3 levels each was employed to systematically optimize drug release profile. Concentration of HPMC K15M (X1) and PVP K30 (X2) were taken as the independent variables and the in vitro dissolution (Y1), t50% (Y2) and mean dissolution time (Y3) as dependent variables. Response surface plots and contour plots were drawn, and the optimum formulations were selected by feasibility and grid searches. Both the polymers had a significant effect on drug release from the tablets. The formulations were followed Higuchi drug kinetics and diffusion was the prime mechanism of drug release. The polynomial mathematical models produce for various response variables using the regression analysis and were found to be statistically significant (P< 0.05). Optimization study was validated using 8 confirmatory runs, indicated very high degree of predictive ability of response surface methodology with mean percentage error 0.197 ± 0.017.The results of multiple linear regression analysis revealed that the sustained release tablets can be prepared using an optimum concentration of HPMC K 15 and PVP K30. Contour plot is presented to represent graphically the effect of the independent variables on the dependent variables selected