title: Agitation Rate and Time for Complete Dissolution in BCS Biowaivers Based on Investigation of a BCS Biowaiver for Dexketoprofen Tablets.
abstract: The objective of the present work is to investigate the validity of the existing requirements for BCS biowaivers of immediate release products containing a class I drug in relation to the agitation rate (50 or 75 rpm in the paddle apparatus) and the time limit for complete dissolution (30 min) in the current biowaivers in vitro dissolution tests. Further, the possibility of extensions will be examined since it has been proposed that the time limit for complete dissolution should be revised to 60 min, and also, if cone formation occurs with apparatus 2 at 50 rpm, then a higher agitation rate is acceptable to eliminate it. The development of four generic dexketoprofen immediate release tablets is described. Dexketoprofen is the eutomer of ketoprofen. According to the BCS, dexketoprofen is a class I drug. Three out of the four products failed to show bioequivalence for Cmax in the initial bioequivalence study conducted with the product despite similar but nonrapid dissolution profiles at 50 rpm in the paddle apparatus, or similar and very rapid dissolution profiles at 75 rpm. In conclusion, these data indicate that BCS biowaivers for class I drugs should be granted only when dissolution with the paddle apparatus is complete in 30 min at 50 rpm. The time limit for complete dissolution should not be extended to 60 min. Furthermore, the agitation rate should not be increased to 75 rpm, even in the case of a coning effect.
authors.affiliation: División de Farmacología y Evaluación Clínica, Subdirección de Medicamentos de Uso Humano, Agencia Española de Medicamentos y Productos Sanitarios , 28022 Madrid, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Garcia-Arieta
authors.affiliation: Division of Biopharmaceutics Evaluation, Bureau of Pharmaceutical Sciences, Therapeutic Products Directorate, Health Canada , Ottawa, Ontario K1A 0K9, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Gordon
authors.affiliation: Evaluations and Registration Division, Medicines Control Authority of Zimbabwe , Harare, Zimbabwe.
authors.forename: Luther
authors.initials: L
authors.lastname: Gwaza
authors.affiliation: Pharmacokinetics and Pharmaceutical Technology Area, Engineering Department, Miguel Hernández University , 03560 San Juan de Alicante, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Mangas-Sanjuan
authors.affiliation: Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid , 28040 Madrid, Spain.
authors.forename: Covadonga
authors.initials: C
authors.lastname: Álvarez
authors.affiliation: Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid , 28040 Madrid, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Torrado
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D001702:Biopharmaceutics; D002626:Chemistry, Pharmaceutical; D006801:Humans; D007660:Ketoprofen / Q000031:analogs & derivatives* / Q000737:chemistry; D012995:Solubility; D013607:Tablets / Q000737:chemistry*; D013810:Therapeutic Equivalency; D014325:Tromethamine / Q000737:chemistry*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013607:Tablets; D014325:Tromethamine; D007660:Ketoprofen; C118296:dexketoprofen trometamol
keywords: BCS class I; bioequivalence; biowaiver; dexketoprofen; in vitro dissolution