title: Evaluation of a three compartment in vitro gastrointestinal simulator dissolution apparatus to predict in vivo dissolution.
abstract: In vitro dissolution tests are performed for new formulations to evaluate in vivo performance, which is affected by the change of gastrointestinal (GI) physiology, in the GI tract. Thus, those environmental changes should be introduced to an in vitro dissolution test. Many studies have successfully shown the improvement of in vitro-in vivo correlations (IVIVC) by introducing those physiological changes into dissolution tests. The gastrointestinal simulator (GIS), a multicompartment in vitro dissolution apparatus, was developed to evaluate in vivo drug dissolution. A gastric-emptying rate along with transit rate are key factors to evaluate in vivo drug dissolution and, hence, drug absorption. Dissolution tests with the GIS were performed with Biopharmaceutical Classification System class I drugs at five different gastric-emptying rates in the fasted state. Computational models were used to determine in vivo gastric-emptying time for propranolol and metoprolol based on the GIS dissolution results. Those were compared with published clinical data to determine the gastric half-emptying time. In conclusion, the GIS is a practical tool to assess dissolution properties and can improve IVIVC.
authors.affiliation: College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065; Pharmacokinetics group, Sawai Pharmaceutical Company, Ltd, Osaka 532-0003, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Takeuchi
authors.affiliation: College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsume
authors.affiliation: College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Amidon
authors.affiliation: College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065. Electronic address: glamidon@med.umich.edu.
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Amidon
mesh_terms: D002626:Chemistry, Pharmaceutical; D004386:Duodenum / Q000502:physiology*; D004867:Equipment Design; D005215:Fasting; D065570:Gastric Absorption; D005746:Gastric Emptying; D005772:Gastrointestinal Transit; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D007583:Jejunum / Q000502:physiology*; D007700:Kinetics; D008422:Materials Testing; D008790:Metoprolol / Q000737:chemistry*; D008954:Models, Biological; D008956:Models, Chemical; D011433:Propranolol / Q000737:chemistry*; D012995:Solubility; D013270:Stomach / Q000502:physiology*; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000295:instrumentation*
chemical_list: D013607:Tablets; D011433:Propranolol; D008790:Metoprolol
keywords: ASD; Dissolution rate; GIS; GastroPlus; In vitro models; Transit time; dissolution; gastric emptying; in vitro/in vivo correlations (IVIVC); Gastrointestinal transit