title: Enhanced absorption of the poorly soluble drug fenofibrate by tuning its release rate from ordered mesoporous silica.
abstract: The aim of the present study was to evaluate the effect of release rate from ordered mesoporous silica materials on the rate and extent of absorption of the poorly soluble drug fenofibrate. Three ordered mesoporous silica materials with different pore diameter (7.3 nm, 4.4 nm and 2.7 nm) were synthesized and loaded with fenofibrate via impregnation. Release experiments were conducted under sink conditions and under supersaturating conditions in biorelevant media, simulating the fasted and the fed state. Subsequently, all silica-based formulations were evaluated in vivo (rat model). The release experiments under sink conditions indicated a clear increase in release rate with increasing pore size. However, under supersaturating conditions (FaSSIF), the, pharmaceutical performance (in terms of both the degree and duration of supersaturation), increased with decreasing pore size. The same trend was observed in vivo (fasted state): the area under the plasma concentration-time profile amounted to 102 ± 34 μMh, 86 ± 19 μMh and 20 ± 13 μMh for the materials with pore diameter of 2.7 nm, 4.4 nm and 7.3 nm, respectively. The results of this, study demonstrate that a decrease in drug release rate - and thus, a decrease of the rate at which supersaturation is created - is beneficial to the absorption of fenofibrate.
authors.affiliation: Laboratory for Pharmacotechnology and Biopharmacy, Katholieke Universiteit Leuven, Building O&N2, Herestraat 49-box 921, BE-3000 Leuven, Belgium.
authors.forename: Michiel
authors.initials: M
authors.lastname: Van Speybroeck
authors.forename: Randy
authors.initials: R
authors.lastname: Mellaerts
authors.forename: Raf
authors.initials: R
authors.lastname: Mols
authors.forename: Thao Do
authors.initials: TD
authors.lastname: Thi
authors.forename: Johan Adriaan
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: D000042:Absorption; D000818:Animals; D002626:Chemistry, Pharmaceutical; D011345:Fenofibrate / Q000737:chemistry* / Q000493:pharmacokinetics*; D004364:Pharmaceutical Preparations; D016062:Porosity; D051381:Rats; D017208:Rats, Wistar; D012822:Silicon Dioxide / Q000737:chemistry*; D012995:Solubility
chemical_list: D004364:Pharmaceutical Preparations; D012822:Silicon Dioxide; D011345:Fenofibrate