title: Use of ordered mesoporous silica to enhance the oral bioavailability of ezetimibe in dogs.
abstract: The aim of this study was to investigate the bioavailability enhancement of the biopharmaceutics classification system class II compound ezetimibe loaded in ordered mesoporous silica (OMS) in dogs. The OMS was characterized as highly ordered mesoporous material with a narrow pore size distribution. Ezetimibe was loaded in OMS via incipient wetness impregnation to obtain a 20% (w/w) drug load, characterized by nitrogen adsorption and differential scanning calorimetry, and formulated in one capsule and two tablet formulations. Physicochemical characterization of loaded OMS indicated that ezetimibe molecules were molecularly deposited on the hydrophilic surface of the OMS. Two in vitro dissolution experiments were performed at 37°C in simulated gastric fluid with 0.1% sodium lauryl sulfate or Tween 80 to determine the drug release. All concepts were compared in vitro and in vivo with the commercially available tablet Ezetrol®. A dog study was designed to determine the oral bioavailability of ezetimibe capsules and tablets. The tablet preparations showed similar results to that of Ezetrol®. The capsule formulation demonstrated a faster absorption into the blood circulation, including a superior metabolization of ezetimibe into the active glucuronide conjugate. In vivo evaluation in dogs confirmed the improvement of ezetimibe absorption with the use of OMS as drug delivery technology.
authors.affiliation: Formac Pharmaceuticals, Leuven, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Kiekens
authors.forename: Siemon
authors.initials: S
authors.lastname: Eelen
authors.forename: Loes
authors.initials: L
authors.lastname: Verheyden
authors.forename: Tinne
authors.initials: T
authors.lastname: Daems
authors.forename: Johan
authors.initials: J
authors.lastname: Martens
authors.forename: Guy
authors.initials: G
authors.lastname: Van Den Mooter
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001384:Azetidines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry*; D000069438:Ezetimibe; D008297:Male; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D012995:Solubility
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D004337:Drug Carriers; D012822:Silicon Dioxide; D000069438:Ezetimibe