title: Impregnation of Fenofibrate on mesoporous silica using supercritical carbon dioxide.
abstract: Low oral bioavailability can be circumvented by the formulation of the poorly water soluble drug in ordered mesoporous silica (OMS-L-7). Fenofibrate is an orally administered, poorly water-soluble active pharmaceutical ingredient (API), used clinically to lower lipid levels. Fenofibrate was loaded into silica using two methods: incipient wetness and supercritical impregnation. This study investigates the impact of loading and the impact of varying supercritical carbon dioxide (scCO2) processing conditions. The objective is to enhance Fenofibrate loading into silica while reducing degree of the drug crystallinity, so as to increase the drug's dissolution rate and its bioavailability. The comparison of both impregnation processes was made in terms of impregnation yields and duration as well as physical characterization of the drug. While incipient wetness method led to a Fenofibrate loading up to 300 mgdrug/gsilica in 48 h of impregnation, the supercritical impregnation method yielded loading up to 485 mgdrug/gsilica in 120 min of impregnation duration, at 16 MPa and 308 K, with a low degree of crystallinity (about 1%) comparable to the crystallinity observed via the solvent method. In addition to the enhancement of impregnation efficiency, the supercritical route provides a solvent-free alternative for impregnation.
authors.affiliation: Aix Marseille Université, CNRS, Centrale Marseille, M2P2 UMR 7340, 13451 Marseille, France. Electronic address: abir.gch@hotmail.fr.
authors.forename: Abir
authors.initials: A
authors.lastname: Bouledjouidja
authors.affiliation: Aix Marseille Université, CNRS, Centrale Marseille, M2P2 UMR 7340, 13451 Marseille, France. Electronic address: yasmine.masmoudi@univ-amu.fr.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Masmoudi
authors.affiliation: FORMAC Pharmaceuticals NV, Gaston Geenslaan 1, 3001 Heverlee, Belgium.
authors.forename: Michiel
authors.initials: M
authors.lastname: Van Speybroeck
authors.affiliation: FORMAC Pharmaceuticals NV, Gaston Geenslaan 1, 3001 Heverlee, Belgium.
authors.forename: Laurent
authors.initials: L
authors.lastname: Schueller
authors.affiliation: Aix Marseille Université, CNRS, Centrale Marseille, M2P2 UMR 7340, 13451 Marseille, France. Electronic address: elisabeth.badens@univ-amu.fr.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Badens
mesh_terms: D001682:Biological Availability; D002245:Carbon Dioxide / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D011345:Fenofibrate / Q000008:administration & dosage* / Q000737:chemistry; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013997:Time Factors
chemical_list: D000960:Hypolipidemic Agents; D012997:Solvents; D002245:Carbon Dioxide; D012822:Silicon Dioxide; D011345:Fenofibrate
keywords: Drug delivery system; Fenofibrate; Ordered mesoporous silica (OMS-L-7); Soaking in liquid; Supercritical fluids