title: Ordered mesoporous silica to enhance the bioavailability of poorly water-soluble drugs: Proof of concept in man.
abstract: Formulating poorly water soluble drugs using ordered mesoporous silica materials is an emerging approach to tackle solubility-related bioavailability problems. The current study was conducted to assess the bioavailability-enhancing potential of ordered mesoporous silica in man. In this open-label, randomized, two-way cross-over study, 12 overnight fasted healthy volunteers received a single dose of fenofibrate formulated with ordered mesoporous silica or a marketed product based on micronized fenofibrate. Plasma concentrations of fenofibric acid, the pharmacologically active metabolite of fenofibrate, were monitored up to 96h post-dose. The rate (Cmax/dose increased by 77%; tmaxreduced by 0.75h) and extent of absorption (AUC0-24h/dose increased by 54%) of fenofibrate were significantly enhanced following administration of the ordered mesoporous silica based formulation. The results of this study serve as a proof of concept in man for this novel formulation approach.
authors.affiliation: Laboratory for Pharmaceutical Technology and Biopharmacy, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium; Department of Chemical Engineering, Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia. Electronic address: katarinabukara@gmail.com.
authors.forename: Katarina
authors.initials: K
authors.lastname: Bukara
authors.affiliation: Formac Pharmaceuticals NV, Gaston Geenslaan 1, B-3001 Heverlee, Belgium.
authors.forename: Laurent
authors.initials: L
authors.lastname: Schueller
authors.affiliation: Formac Pharmaceuticals NV, Gaston Geenslaan 1, B-3001 Heverlee, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Rosier
authors.affiliation: Formac Pharmaceuticals NV, Gaston Geenslaan 1, B-3001 Heverlee, Belgium.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Martens
authors.affiliation: Formac Pharmaceuticals NV, Gaston Geenslaan 1, B-3001 Heverlee, Belgium.
authors.forename: Tinne
authors.initials: T
authors.lastname: Daems
authors.affiliation: Formac Pharmaceuticals NV, Gaston Geenslaan 1, B-3001 Heverlee, Belgium.
authors.forename: Loes
authors.initials: L
authors.lastname: Verheyden
authors.affiliation: Formac Pharmaceuticals NV, Gaston Geenslaan 1, B-3001 Heverlee, Belgium.
authors.forename: Siemon
authors.initials: S
authors.lastname: Eelen
authors.affiliation: Formac Pharmaceuticals NV, Gaston Geenslaan 1, B-3001 Heverlee, Belgium.
authors.forename: Michiel
authors.initials: M
authors.lastname: Van Speybroeck
authors.affiliation: W.R. Grace & Co., Incubator Technologies, 7500 Grace Drive, Columbia, MD 21044, United States.
authors.forename: Cristian
authors.initials: C
authors.lastname: Libanati
authors.affiliation: Center for Surface Chemistry and Catalysis, KU Leuven, Kasteelpark Arenberg 23, B-3001 Heverlee, Belgium.
authors.forename: Johan A
authors.initials: JA
authors.lastname: Martens
authors.affiliation: Laboratory of Pharmacotechnology and Biopharmacy, KU Leuven, O&N2, Herestraat 49, Box 921, B-3000 Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Van Den Mooter
authors.affiliation: SGS Lab Simon SA, Vieux Chemin du Poète 10, B-1301 Bierges-Wavre, Belgium.
authors.forename: Françoise
authors.initials: F
authors.lastname: Frérart
authors.affiliation: SGS Belgium NV, Intercity Business Park, Generaal De Wittelaan 19, B-2800 Mechelen, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Jolling
authors.affiliation: SGS Belgium NV, Intercity Business Park, Generaal De Wittelaan 19, B-2800 Mechelen, Belgium.
authors.forename: Marjan
authors.initials: M
authors.lastname: De Gieter
authors.affiliation: Department of Chemical Engineering, Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia.
authors.forename: Branko
authors.initials: B
authors.lastname: Bugarski
authors.affiliation: Laboratory for Pharmaceutical Technology and Biopharmacy, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Kiekens
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D011345:Fenofibrate / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D057230:Limit of Detection; D008297:Male; D008875:Middle Aged; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry*
chemical_list: D014867:Water; D012822:Silicon Dioxide; C006012:fenofibric acid; D011345:Fenofibrate
keywords: Absorption; Bioavailability; Fenofibrate; Ordered mesoporous silica; Solubility