title: Developing dissolution testing methodologies for extended-release oral dosage forms with supersaturating properties. Case example: Solid dispersion matrix of indomethacin.
abstract: The objective of this study was to develop an in vitro dissolution test method with discrimination ability for an extended-release solid dispersion matrix of a lipophilic drug using the United States Pharmacopeia (USP) Apparatus 4, flow-through cell apparatus. In the open-loop configuration, the sink condition was maintained by manipulating the flow rate of the dissolution medium. To evaluate the testing conditions, the drug release mechanism from an extended-release solid dispersion matrix containing hydrophobic and hydrophilic polymers was investigated. As the hydroxypropyl methylcellulose (HPMC) maintained concentrations of indomethacin higher than the solubility in a dissolution medium, the release of HPMC into the dissolution medium was also quantified using size-exclusion chromatography. We concluded that the USP Apparatus 4 is suitable for application to an in vitro dissolution method for orally administered extended-release solid dispersion matrix formulations containing poorly water-soluble drugs.
authors.affiliation: CTM Manufacturing, Astellas Pharma Europe B.V., Leiden 2333 BE, The Netherlands. Electronic address: tomokazu.tajiri@astellas.com.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Tajiri
authors.affiliation: Department of Engineering Science, Osaka Electro-Communication University, Neyagawa, Osaka 572-8530, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Morita
authors.affiliation: Analytical Research Laboratories, Astellas Pharma Inc., Yaizu, Shizuoka 425-0072, Japan.
authors.forename: Ryosaku
authors.initials: R
authors.lastname: Sakamoto
authors.affiliation: Analytical Research Laboratories, Astellas Pharma Inc., Yaizu, Shizuoka 425-0072, Japan.
authors.forename: Hisahi
authors.initials: H
authors.lastname: Mimura
authors.affiliation: Department of Chemistry, School of Science and Technology, Kwansei-Gakuin University, Sanda, Hyogo 669-1337, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Ozaki
authors.affiliation: Faculty of Pharmacy, National & Kapodistrian University of Athens, Panepistimiopolis, 157 71 Zografou, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Reppas
authors.affiliation: Technology Planning & Administration Strategic Planning, Astellas Pharma Inc., Chuo, Tokyo 103-8411, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kitamura
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004304:Dosage Forms; D057927:Hydrophobic and Hydrophilic Interactions; D065347:Hypromellose Derivatives / Q000737:chemistry; D007213:Indomethacin / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004304:Dosage Forms; D011108:Polymers; D014867:Water; D065347:Hypromellose Derivatives; D007213:Indomethacin
keywords: Extended-release solid dispersion; In vitro dissolution test; Indomethacin; Poorly water-soluble drugs; Sink condition; Supersaturation; USP Apparatus 4 (flow-through cell)