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Free Content Determination of rifampicin bioequivalence in a three-drug FDC by WHO and Indian protocols: effect of sampling schedule and size

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SETTING: To promote the quality assurance of fixed-dose combination (FDC) formulations, the World Health Organization (WHO) has prepared a convenient simplified protocol for the determination of rifampicin (RMP) bioequivalence. During the development of this protocol, it was proved that sampling time up to 8 h can determine the rate and extent of RMP absorption. However, this protocol utilises 20 volunteers in contrast to other local regulatory requirements of a minimum of 12 volunteers. The different sample sizes utilised in these protocols may affect the sensitivity of the bioequivalence outcome.

OBJECTIVE: To determine the effect of sampling size and schedule on RMP bioequivalence when two different protocols are used.

DESIGN: A bioequivalence trial was conducted with a study design of 20 volunteers and 24 h sampling time, which fulfils the requirements of both the WHO and Indian regulatory protocols. Pharmacokinetic and statistical analysis was done by stepwise reduction in sample size and schedule.

RESULT: Bioequivalence limits of RMP were unaffected by a reduced sample size of 12 volunteers and 8 h sampling time.

CONCLUSION: Minimising sample size after validation for borderline and poor quality FDC formulations can further reduce the cost of conducting bioequivalence trials.

Keywords: bioequivalence; fixed-dose combination; rifampicin; tuberculosis

Document Type: Regular Paper

Affiliations: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Nagar, India

Publication date: January 1, 2005

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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