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Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Ribavirin
Navid Goodarzi1, Ahmadreza Barazesh Morgani2, Bertil Abrahamsson3
1Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Journal of Pharmaceutical Sciences
|March 9, 2016
Summary
This study reviews data for waiving in vivo bioequivalence (BE) testing for ribavirin immediate-release oral forms. Despite a narrow therapeutic index, risks of bioequivalence issues appear low, suggesting biowaivers may be considered.
Area of Science:
- Pharmaceutical Sciences
- Drug Development
- Regulatory Science
Background:
- Ribavirin is a highly soluble drug with undefined permeability, suggesting Biopharmaceutical Classification System (BCS) Class III assignment.
- Intestinal absorption of ribavirin involves saturable uptake via the hCNT2 transporter.
- Ribavirin is classified as a narrow therapeutic index (NTI) drug.
Purpose of the Study:
- To review literature data supporting a waiver of in vivo bioequivalence (BE) testing for immediate-release solid oral dosage forms of ribavirin.
- To assess the risks and benefits of granting a biowaiver for ribavirin products.
Main Methods:
- Literature review of existing data on ribavirin solubility, permeability, absorption, and excipient interactions.
- Evaluation of ribavirin's characteristics against Biopharmaceutical Classification System (BCS) criteria.
- Assessment of potential risks for bioinequivalence based on formulation and manufacturing variables.
Main Results:
- Ribavirin's high solubility and BCS Class III characteristics are noted.
- No common excipients have demonstrated competition for ribavirin absorption.
- No reported issues of bioequivalence for ribavirin formulations with varying excipients or manufacturing methods.
- Despite NTI status precluding a standard BCS-based biowaiver, the risk of bioinequivalence appears low.
Conclusions:
- The risk of bioinequivalence for immediate-release ribavirin oral dosage forms seems low, even with different excipients and manufacturing processes.
- While ribavirin's narrow therapeutic index typically prevents biowaivers, the potential risks of in vivo BE studies in healthy subjects warrant consideration.
- A careful risk-benefit assessment is needed when considering biowaivers for ribavirin products.
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