Biowaiver monographs for immediate release solid oral dosage forms: rifampicin

Area of Science:

• Pharmaceutical Sciences
• Drug Regulatory Affairs

Background:

• Rifampicin is an Active Pharmaceutical Ingredient (API) used in immediate-release (IR) solid oral dosage forms.
• Its physicochemical properties classify it as a BCS Class II drug (low solubility, high permeability).
• Previous studies have reported bioavailability (BA) and bioequivalence (BE) issues with rifampicin formulations.

Purpose of the Study:

• To review literature data regarding the suitability of waiving in vivo bioequivalence (BE) testing for rifampicin IR solid oral dosage forms.
• To assess the potential for biowaiver approval for new multisource or reformulated rifampicin products.

Main Methods:

• Literature review of rifampicin's solubility, permeability, therapeutic index, pharmacokinetics, and excipient interactions.
• Analysis of reported BE/BA problems and studies on in vitro dissolution predictive capabilities.
• Evaluation of data relevant to the Biopharmaceutics Classification System (BCS).

Main Results:

• Rifampicin exhibits low solubility and high permeability, consistent with BCS Class II.
• Numerous reports detail failures of rifampicin IR solid oral dosage forms to meet BE standards.
• The underlying reasons for these BE failures remain poorly understood.
• No in vitro dissolution data were found to reliably predict product nonequivalence.

Conclusions:

• A biowaiver for rifampicin IR solid oral dosage forms is not recommended.
• This applies to both new multisource products and significant post-approval changes to existing formulations.
• Further research is needed to understand rifampicin BE issues and establish predictive dissolution methods.