Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Ondansetron |
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| Affiliation: | 1. Faculty of Medicine, Institute of Preclinical and Clinical Pharmacology & Toxicology, Skopje, Republic of Macedonia;2. SDC Slovenia, Lek Pharmaceuticals d.d., Ljubljana 1529, Slovenia;3. AstraZeneca Pharmaceutics, R&D, Mölndal, Sweden;4. Brazilian Health Surveillance Agency (Anvisa), Division of Bioequivalence, Brasilia, Brazil;5. RIVM (National Institute for Public Health and the Environment), Bilthoven, The Netherlands;6. World Health Organization, Geneva, Switzerland;7. Institute of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg – University, Mainz, Germany;8. Center for Drug Evaluation and Research, Office of Clinical Pharmacology, US Food and Drug Administration, Maryland;9. Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland;10. International Pharmaceutical Federation (FIP), The Hague, The Netherlands;11. Institute of Pharmaceutical Technology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany;1. PHAST GmbH, Homburg, Germany;2. Department of Pharmaceutical Technology and Biopharmaceutics, Johannes Gutenberg University, Mainz, Germany;3. International Pharmaceutical Federation, The Hague, The Netherlands;4. Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland;5. Center for Drug Evaluation and Research, Office of Clinical Pharmacology, US Food and Drug Administration, Maryland;6. RIVM-National Institute for Public Health and the Environment, Bilthoven, The Netherlands;7. Brazilian Health Surveillance Agency (Anvisa), Division of Bioequivalence, Brasilia, Brazil;8. AstraZeneca R&D, Mölndal, Sweden;9. Institute of Pharmaceutical Technology, J.W. Goethe University, Frankfurt am Main, Germany |
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| 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 (IR) solid oral dosage form can be approved based on a Biopharmaceutics Classification System (BCS)-based biowaiver. Ondansetron, a 5HT3 receptor antagonist, is used at doses ranging from 4 mg 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. Furthermore, ondansetron hydrochloride 8 mg IR tablets (Zofran® 8 mg) and multiples thereof (16 mg = Zofran® 8 mg × 2 tablets and 24 mg = Zofran® 8 mg × 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 IR tablets. |
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| Keywords: | ondansetron hydrochloride dihydrate biowaiver solubility permeability biopharmaceutics classification system (BCS) dissolution |
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