Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Ondansetron

Area of Science:

• Pharmaceutical Sciences
• Pharmacokinetics
• Drug Development

Background:

• Ondansetron is a 5HT3 receptor antagonist used to manage chemotherapy, radiotherapy, and postoperative nausea and vomiting.
• It is administered orally in doses of 4-24 mg.
• Ondansetron hydrochloride dihydrate exhibits pH-dependent solubility as a weak base.

Purpose of the Study:

• To evaluate ondansetron hydrochloride dihydrate's suitability for a Biopharmaceutics Classification System (BCS)-based biowaiver.
• To determine if immediate-release (IR) solid oral dosage forms can be approved based on BCS criteria.

Main Methods:

• Review of literature data on physicochemical, pharmaceutical, and pharmacokinetic properties.
• Assessment of solubility and permeability according to BCS guidelines.
• Evaluation of dissolution testing results for ondansetron hydrochloride 8 mg IR tablets.

Main Results:

• Ondansetron hydrochloride dihydrate meets the criteria for "high solubility" and "high permeability", classifying it as a BCS Class I drug.
• Ondansetron hydrochloride 8 mg IR tablets and higher doses (16 mg, 24 mg) meet "rapidly dissolving" criteria.
• The drug possesses a wide therapeutic window and is well-tolerated orally.

Conclusions:

• The favorable physicochemical and pharmacokinetic profile supports the use of a BCS-based biowaiver for ondansetron hydrochloride dihydrate IR tablets.
• The minimal risks associated with bioequivalence decisions further support this recommendation.
• Marketing authorization for IR solid oral dosage forms can be considered based on BCS principles.