FORMULATION DEVELOPMENT AND OPTIMIZATION OF BILAYER SUSTAINED RELEASE MATRIX TABLETS OF VALSARTAN USING 32 FACTORIAL DESIGN

ABSTRACTThe development of bilayered sustained release tablets of Valsartan acetate aimed to provide acontrolled drug release profile with a fast-releasing loading dose and a sustained-maintenancedose. The tablets were formulated using wet granulation, incorporating Eudragit RSPO andEudragit RLPO as polymers, and sodium starch glycolate as a super disintegrant. Drug-polymerinteractions were studied using FTIR providing critical insights for formulation optimization.The granules and tablets underwent extensive evaluation for pre- and post-compressionparameters, including angle of repose, compressibility index, Hausner’s ratio, tablet hardness,friability, weight variation, drug content, and in vitro dissolution, with satisfactory results. A 32full factorial design was employed to optimize the drug release, with Eudragit RSPO (X1) andEudragit RLPO (X2) as independent variables and the time to achieve 90% drug dissolution(t90%) as the dependent variable. Multiple regression analysis identified the optimal levels of thepolymers for achieving the desired release profile. A checkpoint batch, formulated to validate themathematical model, showed a high degree of accuracy (p = 0.0079). Formulation F6, whichexhibited the highest f2 value (86.33) and a t90% closest to the checkpoint batch, was selected asthe optimized formulation. Kinetic analysis of in vitro release data revealed that the optimizedbatch followed zero-order, non-Fickian diffusion. These findings suggest that the bilayeredValsartan tablets offer an effective strategy for sustained drug delivery with predictablepharmacokinetic behavior.