title: In Vivo Performance of Fenofibrate Formulated With Ordered Mesoporous Silica Versus 2-Marketed Formulations: A Comparative Bioavailability Study in Beagle Dogs.
abstract: The present study aims to evaluate the in vitro and in vivo performance of ordered mesoporous silica (OMS) as a carrier for the poorly water-soluble compound fenofibrate. Fenofibrate was loaded into OMS via incipient wetness impregnation to obtain a 29% drug load and formulated into capsules. Two capsule dosage forms (containing 33.5 and 16.75 mg fenofibrate, respectively) were compared with the commercially available forms-Lipanthyl(®) (fenofibrate microcrystals) and Tricor(®) (fenofibrate nanocrystals). In vitro dissolution tests showed that the amount of fenofibrate released from Lipanthyl(®) and Tricor(®) was approximately 30%, whereas approximately 66% and 60% of the drug was released from OMS capsules containing 33.5 and 16.75 mg of fenofibrate, respectively. Storage of OMS capsules loaded with 33.5 mg of fenofibrate at 25°C/60% relative humidity (RH) or 40°C/75% RH did not alter the release kinetics, nor the physical state of the compound, pointing the stability of the present formulation. The in vivo study in dogs confirmed satisfying level of safety and tolerability of fenofibrate-OMS formulation (eq. 33.5 mg) with the potential to improve the absorption of fenofibrate. Though some variability in the data, this formulation is promising to be further investigated in a clinical trial setting.
authors.affiliation: Laboratory for Pharmaceutical Technology and Biopharmacy, University of Antwerp, Universiteitsplein 1, Wilrijk B-2610, 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, Heverlee B-3001, Belgium.
authors.forename: Laurent
authors.initials: L
authors.lastname: Schueller
authors.affiliation: Formac Pharmaceuticals NV, Gaston Geenslaan 1, Heverlee B-3001, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Rosier
authors.affiliation: Formac Pharmaceuticals NV, Gaston Geenslaan 1, Heverlee B-3001, Belgium.
authors.forename: Tinne
authors.initials: T
authors.lastname: Daems
authors.affiliation: Formac Pharmaceuticals NV, Gaston Geenslaan 1, Heverlee B-3001, Belgium.
authors.forename: Loes
authors.initials: L
authors.lastname: Verheyden
authors.affiliation: Formac Pharmaceuticals NV, Gaston Geenslaan 1, Heverlee B-3001, Belgium.
authors.forename: Siemon
authors.initials: S
authors.lastname: Eelen
authors.affiliation: Center for Surface Chemistry and Catalysis, KU Leuven, Kasteelpark Arenberg 23, Heverlee B-3001, Belgium.
authors.forename: Johan A
authors.initials: JA
authors.lastname: Martens
authors.affiliation: Drug Delivery and Disposition, University of Lueven (KU Leuven), O&N2, Herestraat 49, box 921, Leuven B-3000, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Van den Mooter
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, Wilrijk B-2610, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Kiekens
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D011345:Fenofibrate / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D000960:Hypolipidemic Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D012995:Solubility
chemical_list: D004337:Drug Carriers; D000960:Hypolipidemic Agents; D012822:Silicon Dioxide; D011345:Fenofibrate
keywords: dissolution; fenofibrate; oral bioavailability; ordered mesoporous silica; poor solubility