Formulation development and evaluation of Diltiazem HCl sustained release matrix tablets using HPMC K4M and K100M

Abstract

The aim of this study was to develop a sustained release hydrophilic matrix tablet of Diltiazem HCl and evaluates the effect of formulation variables (e.g. lubricant, binder, polymer content and viscosity grades of HPMC) on drug release. Twelve different formulations (F1-F12) were prepared by direct compression. The results of the physical parameters and assay were found to be within the acceptable range. Rate of drug release was found to be slow as the fraction of the polymer was increased from 20-50%. The drug release rate from tablets containing K4M was effectively controlled by increasing the talc concentration, whereas the burst effect was reduced by increasing binder content. The drug release was higher with K4M as compare to K100M. Model-dependent and independent methods were used for data analysis and the best results were observed for K4M in Higuchi (R2 =0.9903-0.9962) and K100M in Baker and Lonsdale (R2 =0.9779-0.9941). The release mechanism of all formulations was non-Fickian. F7 (50% K4M, 2% talc, 10% Avicel PH101) and F11 (40% K100M) were very close to targeted release profile. F12 (50% K100M) exhibited highest degree of swelling and lowest erosion. The f1 and f2 test were performed taking F11 as a reference formulation.