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...

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Bibliographic Details
Published in:International journal of pharmaceutics 2004-12, Vol.287 (1), p.97-112
Main Authors: Agrawal, Shrutidevi, Panchagnula, Ramesh
Format: Article
Language:English
Subjects:
Bioavailability
Bioequivalence
Biological and medical sciences
Biological Availability
Chemistry, Pharmaceutical
Dissolution
Fixed dose combination
General pharmacology
Humans
Hydrogen-Ion Concentration
Medical sciences
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Rifampicin
Rifampin - administration & dosage
Rifampin - chemistry
Rifampin - pharmacokinetics
Solubility
Therapeutic Equivalency
Tuberculosis
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Summary: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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2004.09.005