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

Abstract Literature data pertaining to the physicochemical, pharmaceutical and pharmacokinetic properties of ondansetron hydrochloride dihydrate are reviewed to arrive at a decision on whether a marketing authorization of an immediate release solid oral dosage form can be approved based on a BCS-based biowaiver. Ondansetron, a 5HT 3 receptor antagonist, is used at doses ranging from 4mg to 24 mg in the management of nausea and vomiting associated with chemotherapy, radiotherapy and postoperative treatment. It is a weak base and thus exhibits pH dependent solubility. However, it is able to meet the criteria of ‘high solubility’ as well as ‘high permeability’ and can therefore be classified as a BCS class I drug. Further, ondansetron hydrochloride 8mg IR tablets (Zofran 8 mg) and multiples thereof (16 mg =Zofran 8mg × 2 tablets and 24 mg =Zofran 8mg × 3 tablets) meet the criteria of ‘rapidly dissolving’ in dissolution testing. Ondansetron hydrochloride has a wide therapeutic window and is well-tolerated after oral administration. Based on its favorable physicochemical properties, pharmacokinetic data and the minimal risks associated with an incorrect bioequivalence decision, the BCS-based biowaiver procedure can be recommended for ondansetron hydrochloride dihydrate immediate release tablets.