Enhanced absorption of the poorly soluble drug fenofibrate by tuning its release rate from ordered mesoporous silica.
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.
Van Speybroeck
Michiel
M
Laboratory for Pharmacotechnology and Biopharmacy, Katholieke Universiteit Leuven, Building O&N2, Herestraat 49-box 921, BE-3000 Leuven, Belgium.
Mellaerts
Randy
R
Mols
Raf
R
Thi
Thao Do
TD
Martens
Johan Adriaan
JA
Van Humbeeck
Jan
J
Annaert
Pieter
P
Van den Mooter
Guy
G
Augustijns
Patrick
P
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
D004364:Pharmaceutical Preparations; D012822:Silicon Dioxide; D011345:Fenofibrate