Biowaiver monographs for immediate release solid oral dosage forms: cimetidine

Area of Science:

• Pharmaceutical Sciences
• Drug Development
• Regulatory Science

Background:

• Cimetidine is an immediate-release (IR) solid oral dosage form.
• Regulatory agencies consider waivers for in vivo bioequivalence (BE) testing to streamline drug approvals.
• The Biopharmaceutics Classification System (BCS) categorizes drugs based on solubility and permeability.

Purpose of the Study:

• To review literature data supporting a waiver of in vivo bioequivalence (BE) testing for cimetidine IR products.
• To evaluate cimetidine's suitability for a biowaiver based on its Biopharmaceutics Classification System (BCS) class, therapeutic index, and excipient interactions.
• To determine conditions under which a biowaiver for cimetidine can be recommended.

Main Methods:

• Literature review of existing data on cimetidine.
• Assessment of cimetidine's classification within the Biopharmaceutics Classification System (BCS).
• Evaluation of cimetidine's pharmacokinetic properties, therapeutic index, and potential excipient interactions.

Main Results:

• Cimetidine is classified as a Biopharmaceutics Classification System (BCS) Class III drug.
• No significant bioavailability (BA) or bioequivalence (BE) problems were reported for cimetidine.
• Data suggests a low risk of excipient interactions with cimetidine.

Conclusions:

• A biowaiver for cimetidine IR products is recommended.
• The biowaiver is contingent upon the test product using specific, commonly reported excipients in usual amounts.
• Both test and comparator products must meet the "rapidly dissolving" criteria as defined by the BCS.