Formulation and Optimization of Extended Release Matrix Tablets of Losartan Potassium Using Response Surface Methodology (RSM)

The aim of this research work was to formulate and systematically evaluate in vitro performance of extended release matrix tablets of Losartan potassium. Tablets were prepared by direct compression method, applying Response Surface Methodology (RSM) by incorporating a 3-factor, 2-level Box-Behnken statistical design. Independent variables are the release retardant polymers such as HPMC K4M (X1), ethyl cellulose (X2), and sodium carboxy methyl cellulose(X3) and dependent variables are the percentage drug release in 0.1N HCL for 2 hours (Y1) and in 6.8 Phosphate buffer up to 24 hours (Y2) were studied. The Validation and optimization of study with 17 confirmatory runs indicated high degree of prophetic ability of response surface methodology with mean percentage error (± SD) as 1.54 ± 2.87% and 2.27 ± 1.36% drug release in 0.1N HCL and buffer. The physical evaluation and in vitro release studies were performed on all the formulations and the data were fitted to different release kinetic equations. The optimized formulation depicted a release of 16.98% and 96.26% from 0.1N HCL and buffer solutions at 24 hours. Point prediction tool of design expert software (version 8.0.1), RSM, shows 17.71% and 95.72% validity of the predicted model for drug release from 0.1N HCL and buffer solutions respectively. The optimized formulation follows Higuchi model and first order release kinetics which shows non-fickian type of release. Applying RSM, with few runs, effective extended release formulation of Losartan potassium was developed.