title: Increasing the oral bioavailability of the poorly water soluble drug itraconazole with ordered mesoporous silica.
abstract: This study aims to evaluate the in vivo performance of ordered mesoporous silica (OMS) as a carrier for poorly water soluble drugs. Itraconazole was selected as model compound. Physicochemical characterization was carried out by SEM, TEM, nitrogen adsorption, DSC, TGA and in vitro dissolution. After loading itraconazole into OMS, its oral bioavailability was compared with the crystalline drug and the marketed product Sporanox in rabbits and dogs. Plasma concentrations of itraconazole and OH-itraconazole were determined by HPLC-UV. After administration of crystalline itraconazole in dogs (20mg), no systemic itraconazole could be detected. Using OMS as a carrier, the AUC0-8 was boosted to 681+/-566 nM h. In rabbits, the AUC0-24 increased significantly from 521+/-159 nM h after oral administration of crystalline itraconazole (8 mg) to 1069+/-278 nM h when this dose was loaded into OMS. Tmax decreased from 9.8+/-1.8 to 4.2+/-1.8h. No significant differences (AUC, Cmax, and Tmax) could be determined when comparing OMS with Sporanox in both species. The oral bioavailability of itraconazole formulated with OMS as a carrier compares well with the marketed product Sporanox, in rabbits as well as in dogs. OMS can therefore be considered as a promising carrier to achieve enhanced oral bioavailability for drugs with extremely low water solubility.
authors.affiliation: Centre for Surface Chemistry and Catalysis, Catholic University of Leuven, Heverlee, Belgium.
authors.forename: Randy
authors.initials: R
authors.lastname: Mellaerts
authors.forename: Raf
authors.initials: R
authors.lastname: Mols
authors.forename: Jasper A G
authors.initials: JA
authors.lastname: Jammaer
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Aerts
authors.forename: Pieter
authors.initials: P
authors.lastname: Annaert
authors.forename: Jan
authors.initials: J
authors.lastname: Van Humbeeck
authors.forename: Guy
authors.initials: G
authors.lastname: Van den Mooter
authors.forename: Patrick
authors.initials: P
authors.lastname: Augustijns
authors.forename: Johan A
authors.initials: JA
authors.lastname: Martens
mesh_terms: D000284:Administration, Oral; D000327:Adsorption; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D004285:Dogs; D004337:Drug Carriers; D017964:Itraconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009584:Nitrogen / Q000737:chemistry; D016062:Porosity; D011817:Rabbits; D012822:Silicon Dioxide / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D014867:Water; D017964:Itraconazole; D012822:Silicon Dioxide; D009584:Nitrogen