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Biowaiver monograph for immediate-release solid oral dosage forms: fluconazole.
Naseem Charoo1, Rodrigo Cristofoletti2, Alexandra Graham3
1AlFalah Life Sciences Pvt. Ltd., Wathora, Budgam, India.
Journal of Pharmaceutical Sciences
|October 15, 2014
Summary
A biowaiver for fluconazole immediate-release dosage forms is recommended, reducing the need for in vivo bioequivalence testing. This is supported by fluconazole's properties and specific in vitro study guidelines.
Area of Science:
- Pharmaceutical Sciences
- Drug Development
- Regulatory Science
Background:
- Fluconazole is an antifungal agent used in immediate-release (IR) solid oral dosage forms.
- Regulatory agencies evaluate bioequivalence (BE) testing requirements for drug product approval.
- Waivers for in vivo BE testing can streamline the approval process for certain drug products.
Purpose of the Study:
- To review literature data supporting a waiver of in vivo bioequivalence (BE) testing for fluconazole IR dosage forms.
- To determine the conditions under which a biowaiver can be safely recommended for fluconazole.
- To assess the risk of bioinequivalence for fluconazole IR products based on available data.
Main Methods:
- Literature review of data related to solubility, dissolution, permeability, therapeutic index, pharmacokinetics, and pharmacodynamics of fluconazole.
- Analysis of biopharmaceutics classification system (BCS) data for fluconazole.
- Evaluation of drug-excipient interaction data and BE/bioavailability (BA) issues.
Main Results:
- Fluconazole is a BCS Class I drug (polymorphic forms II and III) with a wide therapeutic index.
- The risk of bioinequivalence due to formulation and manufacturing is generally low for fluconazole IR products.
- In vitro studies, when conducted according to biowaiver guidelines, can further reduce this risk.
Conclusions:
- A biowaiver for fluconazole IR dosage forms is recommended under specific conditions.
- Conditions include high solubility of fluconazole (polymorphic form II or III), use of approved excipients, and rapid dissolution profiles.
- Adherence to these criteria ensures product quality and reduces the need for extensive in vivo BE studies.
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