title: Preventing release in the acidic environment of the stomach via occlusion in ordered mesoporous silica enhances the absorption of poorly soluble weakly acidic drugs.
abstract: This study aimed to assess the pharmaceutical performance of formulations consisting of either indomethacin or glibenclamide and the ordered mesoporous silica material SBA-15. Both compounds were loaded on SBA-15 via solvent impregnation. Adsorption in the SBA-15 mesopores was confirmed using nitrogen physisorption. Differential scanning calorimetry results suggested that both compounds were dispersed monomolecularly onto the SBA-15 surface. In in vitro experiments simulating the gastric-to-intestinal transition, the release of both compounds from SBA-15 remained under 1% in simulated gastric fluid (SGF, pH 1.2), whereas both drugs were completely released within 10 min after transfer to fasted state simulated intestinal fluid (FaSSIF, pH 6.5). As both drugs exhibited very rapid precipitation from the supersaturated state in SGF, the preferential release in FaSSIF--where conditions are more favourable by virtue of either much higher solubility (indomethacin) or more stable supersaturation (glibenclamide)--was considered crucial towards achieving optimal absorption. This hypothesis was confirmed by an in vivo study, where the extent of absorption of a glibenclamide-SBA-15 formulation was found to be more than fourfold higher than that of the commercial glibenclamide product Daonil®.
authors.affiliation: Laboratory for Pharmacotechnology and Biopharmacy, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Michiel
authors.initials: M
authors.lastname: van Speybroeck
authors.forename: Randy
authors.initials: R
authors.lastname: Mellaerts
authors.forename: Thao Do
authors.initials: TD
authors.lastname: Thi
authors.forename: Johan A
authors.initials: JA
authors.lastname: Martens
authors.forename: Jan
authors.initials: J
authors.lastname: Van Humbeeck
authors.forename: Pieter
authors.initials: P
authors.lastname: Annaert
authors.forename: Guy
authors.initials: G
authors.lastname: Van den Mooter
authors.forename: Patrick
authors.initials: P
authors.lastname: Augustijns
mesh_terms: D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D005753:Gastric Mucosa / Q000378:metabolism*; D005905:Glyburide / Q000008:administration & dosage / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012822:Silicon Dioxide; D012995:Solubility
chemical_list: D004364:Pharmaceutical Preparations; D012822:Silicon Dioxide; D005905:Glyburide; D007213:Indomethacin