Dissolution test as a surrogate for quality evaluation of rifampicin containing fixed dose combination formulations

The present investigation was aimed at developing a dissolution methodology to predict in vivo performance of rifampicin containing fixed dose combination (FDC) products. Six FDC formulations were used in this study, of which four had passed bioequivalence while two failed. Dissolution studies were conducted at agitation intensity of 30-100 rpm as a measure of hydrodynamic stress and at pH media corresponding to gastric and intestinal conditions. Formulations showed variable dissolution at different conditions and dissolution at 50 rpm was most sensitive and differentiated the release profiles of rifampicin under various pH conditions. It was possible to predict in vivo performance of rifampicin from FDCs when in vitro rate and extent of release at various pH was correlated with site, pH and concentration dependent absorption of rifampicin along with gastric emptying time. It was also seen that dissolution conditions recommended in USP for different types of FDCs were insensitive for the formulation changes. Based on this comprehensive evaluation, a decision tree is proposed which will act as a guideline for quality evaluation of FDC products and also will provide a fundamental knowledge for optimization of formulations failing in dissolution studies. (C) 2004 Elsevier B.V. All rights reserved.