title: An understanding of modified release matrix tablets behavior during drug dissolution as the key for prediction of pharmaceutical product performance - case study of multimodal characterization of quetiapine fumarate tablets.
abstract: Motivation for the study was the lack of dedicated and effective research and development (R&D) in vitro methods for oral, generic, modified release formulations. The purpose of the research was to assess multimodal in vitro methodology for further bioequivalence study risk minimization. Principal results of the study are as follows: (i) Pharmaceutically equivalent quetiapine fumarate extended release dosage form of Seroquel XR was developed using a quality by design/design of experiment (QbD/DoE) paradigm. (ii) The developed formulation was then compared with originator using X-ray microtomography, magnetic resonance imaging and texture analysis. Despite similarity in terms of compendial dissolution test, developed and original dosage forms differed in micro/meso structure and consequently in mechanical properties. (iii) These differences were found to be the key factors of failure of biorelevant dissolution test using the stress dissolution apparatus. Major conclusions are as follows: (i) Imaging methods allow to assess internal features of the hydrating extended release matrix and together with the stress dissolution test allow to rationalize the design of generic formulations at the in vitro level. (ii) Technological impact on formulation properties e.g., on pore formation in hydrating matrices cannot be overlooked when designing modified release dosage forms.
authors.affiliation: Institute of Technology, The Pedagogical University of Cracow, ul. Podchorążych 2, 30-084 Kraków, Poland. Electronic address: pkulino@up.krakow.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kulinowski
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Pharmaceutical Faculty, Jagiellonian University, ul. Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Woyna-Orlewicz
authors.affiliation: Physiolution GmbH, Walther-Rathenau-Strasse 49a, 17489 Greifswald, Germany.
authors.forename: Gerd-Martin
authors.initials: GM
authors.lastname: Rappen
authors.affiliation: Department of Biopharmaceutics and Pharmaceutical Technology, Center of Drug Absorption and Transport (C_DAT), Felix-Hausdorff-Str. 3, 17487 Greifswald, Germany.
authors.forename: Dorota
authors.initials: D
authors.lastname: Haznar-Garbacz
authors.affiliation: Department of Magnetic Resonance Imaging, Institute of Nuclear Physics PAN, ul. Radzikowskiego 152, 31-342 Kraków, Poland.
authors.forename: Władysław P
authors.initials: WP
authors.lastname: Węglarz
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Pharmaceutical Faculty, Jagiellonian University, ul. Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Przemysław P
authors.initials: PP
authors.lastname: Dorożyński
mesh_terms: D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D065546:Drug Liberation; D005544:Forecasting; D000069348:Quetiapine Fumarate / Q000737:chemistry* / Q000493:pharmacokinetics*; D012995:Solubility; D013607:Tablets; D055114:X-Ray Microtomography / Q000379:methods*
chemical_list: D003692:Delayed-Action Preparations; D013607:Tablets; D000069348:Quetiapine Fumarate
keywords: Biorelevant dissolution; Magnetic resonance imaging (MRI); Pharmaceutical generic product; Quality by design (QbD); Texture analysis; X-ray microtomography (μCT, Micro-CT)