Biowaiver monographs for immediate release solid oral dosage forms: isoniazid

Area of Science:

• Pharmaceutical Sciences
• Drug Development
• Regulatory Science

Background:

• Isoniazid is a key drug for tuberculosis treatment.
• Evaluating bioequivalence (BE) for immediate-release (IR) solid oral dosage forms is crucial for drug approval.
• The Biopharmaceutics Classification System (BCS) guides decisions on waiving in vivo BE testing.

Purpose of the Study:

• To review literature data for a potential waiver of in vivo bioequivalence (BE) testing for isoniazid IR solid oral dosage forms.
• To assess isoniazid's characteristics (solubility, permeability, pharmacokinetics, excipient interactions) for biowaiver eligibility.

Main Methods:

• Literature review of isoniazid's properties.
• Analysis of Biopharmaceutics Classification System (BCS) data.
• Evaluation of potential excipient interactions and bioavailability issues.

Main Results:

• Isoniazid is highly soluble, but its permeability is inconclusive, placing it on the borderline of BCS Class I and III.
• While most excipients are unlikely to interact, lactose and deoxidizing saccharides may form less permeable condensation products with isoniazid.
• A biowaiver is feasible for IR isoniazid products meeting "very rapidly dissolving" criteria with common excipients.

Conclusions:

• A biowaiver can be granted for IR isoniazid products if they dissolve very rapidly and contain only standard excipients.
• Formulations including lactose or other deoxidizing saccharides necessitate in vivo bioequivalence studies.
• Careful consideration of excipient interactions is vital for regulatory decisions regarding isoniazid drug products.