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Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Cephalexin Monohydrate
Gerlinde F Plöger1, Paul M Quizon2, Bertil Abrahamsson3
1Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany.
Journal of Pharmaceutical Sciences
|April 3, 2020
Summary
Cephalexin monohydrate, a Biopharmaceutics Classification System Class 1 drug, can be approved without human bioequivalence studies. This scientifically justified biowaiver requires specific dissolution criteria and well-established excipients.
Area of Science:
- Pharmaceutical Sciences
- Drug Development
- Regulatory Science
Background:
- Immediate release solid oral dosage forms require bioequivalence studies for approval.
- Waivers for these studies are possible under specific conditions, simplifying drug approval processes.
Purpose of the Study:
- To evaluate the scientific justification for waiving in vivo bioequivalence studies for cephalexin monohydrate.
- To assess cephalexin monohydrate's suitability for biowaiver based on its physicochemical properties and existing data.
Main Methods:
- Literature review of solubility, permeability, pharmacokinetic data, and bioequivalence studies.
- Solubility and degradation studies considering various pH values.
- Dissolution studies under Biopharmaceutics Classification System-biowaiver conditions for the drug and generic formulations.
Main Results:
- Cephalexin monohydrate is classified as a Biopharmaceutics Classification System Class 1 drug, indicating high solubility and permeability.
- The drug exhibits a wide therapeutic index with no reported bioequivalence issues.
- Dissolution studies confirmed suitability for biowaiver under specified conditions.
Conclusions:
- Biowaiver-based approval for cephalexin monohydrate products is scientifically sound.
- Approval is contingent upon using well-established excipients and meeting rapid or very rapid dissolution criteria.
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