title: Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Nifedipine.
abstract: Literature data relevant to the biopharmaceutical properties of the active pharmaceutical ingredient (API) nifedipine are reviewed to evaluate whether a waiver of in vivo bioequivalence (BE) testing of immediate-release (IR) dosage forms formulated as tablets and soft gelatin capsules is warranted. Nifedipine's solubility and permeability, its therapeutic use and index, pharmacokinetics, food drug interactions, and any reported BE/bioavailability problems were all taken into consideration. Solubility and BA data indicate conclusively that nifedipine is a class II substance of biopharmaceutics classification system (BCS) and that the formulation of drug product plays a key role on the dissolution characteristics of the API. Therefore, a BCS biowaiver-based approval of nifedipine containing IR oral dosage forms cannot be recommended for reformulated/new multisource drug products or for major scale-up and postapproval changes to the existing drug products.
authors.affiliation: PHAST GmbH, Homburg, Germany.|Department of Pharmaceutical Technology and Biopharmaceutics, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Jayachandar
authors.initials: J
authors.lastname: Gajendran
authors.affiliation: PHAST GmbH, Homburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Krämer
authors.affiliation: International Pharmaceutical Federation, The Hague, The Netherlands.
authors.forename: Vinod P
authors.initials: VP
authors.lastname: Shah
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Langguth
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland.
authors.forename: James
authors.initials: J
authors.lastname: Polli
authors.affiliation: Center for Drug Evaluation and Research, Office of Clinical Pharmacology, US Food and Drug Administration, Maryland.
authors.forename: Mehul
authors.initials: M
authors.lastname: Mehta
authors.affiliation: RIVM-National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: D W
authors.initials: DW
authors.lastname: Groot
authors.affiliation: Brazilian Health Surveillance Agency (Anvisa), Division of Bioequivalence, Brasilia, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Cristofoletti
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Bertil
authors.initials: B
authors.lastname: Abrahamsson
authors.affiliation: Institute of Pharmaceutical Technology, J.W. Goethe University, Frankfurt am Main, Germany.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Dressman
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D005079:Excipients; D018565:Food-Drug Interactions; D006801:Humans; D007408:Intestinal Absorption; D009543:Nifedipine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D012995:Solubility; D013607:Tablets
chemical_list: D002121:Calcium Channel Blockers; D002214:Capsules; D005079:Excipients; D013607:Tablets; D009543:Nifedipine
keywords: absorption; bioavailability; bioequivalence; dissolution; nifedipine; permeability; soft gelatin capsules; solubility; tablets