Biowaiver monographs for immediate-release solid oral dosage forms: ketoprofen

Area of Science:

• Pharmaceutical Sciences
• Drug Development
• Regulatory Science

Background:

• Ketoprofen is an immediate-release solid oral dosage form.
• Bioequivalence (BE) testing is crucial for drug approval.
• Biopharmaceutics Classification System (BCS) guides drug development.

Purpose of the Study:

• To review literature and experimental data for a biowaiver decision for ketoprofen.
• To assess ketoprofen's suitability for waiving in vivo bioequivalence testing.
• To determine conditions for biowaiver approval of ketoprofen formulations.

Main Methods:

• Literature review of ketoprofen's solubility, permeability, and pharmacokinetics.
• Analysis of excipient interactions and existing bioequivalence/dissolution data.
• Evaluation against Biopharmaceutics Classification System (BCS) criteria and regulatory guidances.

Main Results:

• Ketoprofen is a BCS Class II weak acid.
• Extent of absorption is formulation-independent; rate can be formulation-dependent.
• In vitro dissolution may not fully capture C(max) differences for BCS Class II drugs, but these are acceptable for ketoprofen.

Conclusions:

• A biowaiver for ketoprofen IR solid oral dosage forms is feasible under specific conditions.
• Conditions include approved excipients, rapid dissolution (85% in 30 min at pH 6.8), and similar dissolution profiles across pH values.
• Failure to meet these conditions necessitates in vivo bioequivalence testing.