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