title: In-vivo and in-vitro correlation for delayed-release behaviour of a molsidomine/O-carboxymethyl-O-ethyl-beta-cyclodextrin complex in gastric acidity-controlled dogs.
abstract: The in-vivo absorption behaviour of molsidomine from the delayed-release tablets of an O-carboxymethyl-O-ethyl-beta-cyclodextrin complex was investigated using gastric acidity-controlled dogs under fasted and non-fasted conditions. The in-vitro release profiles were generated by changing the pH of the dissolution medium at different rotation paddle speeds. The absorptivity of molsidomine in the high acidity dog was correlated with the pH-changed release profile (pH 1.2 to 7.0 after 2 h), whereas that in the low acidity dog was correlated with the release profile at a constant pH of 7.0. The absorption in fasted dogs was well correlated with the in-vitro release at the low-rotation paddle speed (< 5 rev min-1), whereas that in the non-fasted dogs was correlated with that of high rotation (100 rev min-1). The present results suggested that the in-vivo delayed-release behaviour of the complex is predictable from the in-vitro release profiles generated using pH-variable dissolution testing apparatus at different rotation speeds of the paddle.
authors.affiliation: Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Horikawa
authors.forename: F
authors.initials: F
authors.lastname: Hirayama
authors.forename: K
authors.initials: K
authors.lastname: Uekama
mesh_terms: D000818:Animals; D003505:Cyclodextrins / Q000737:chemistry* / Q000378:metabolism; D003692:Delayed-Action Preparations; D004285:Dogs; D016503:Drug Delivery Systems / Q000592:standards*; D005215:Fasting; D005744:Gastric Acid / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D008981:Molsidomine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D047392:beta-Cyclodextrins
chemical_list: D003505:Cyclodextrins; D003692:Delayed-Action Preparations; C062590:O-carboxymethyl-O-ethyl-beta-cyclodextrin; D047392:beta-Cyclodextrins; D008981:Molsidomine; C031215:betadex