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Title: Combined use of ordered mesoporous silica and precipitation inhibitors for improved oral absorption of the poorly soluble weak base itraconazole
Authors: Van Speybroeck, Michiel ×
Mols, Rafaƫl
Mellaerts, Randy
Do Thi, Thao
Martens, Johan
Van Humbeeck, Jan
Annaert, Pieter
Van den Mooter, Guy
Augustijns, Patrick #
Issue Date: Aug-2010
Publisher: Wissenschaftliche Verlagsgesellschaft
Series Title: European Journal of Pharmaceutics and Biopharmaceutics vol:75 issue:3 pages:354-365
Abstract: The release of poorly soluble drugs from mesoporous silicates is often associated with the generation of
supersaturation, which implies the risk of drug precipitation and reduced availability for absorption. The
aim of this study was to enhance the in vivo performance of an ordered mesoporous silicate (SBA-15) by
combining it with the precipitation inhibitors hydroxypropylmethylcellulose (HPMC) and hydroxypropylmethylcellulose
acetate succinate (HPMCAS). The poorly soluble weak base itraconazole was used as a
model compound. Formulations were prepared by physically blending itraconazole-loaded SBA-15 with
the precipitation inhibitors. In vitro release experiments implementing a transfer from simulated gastric
fluid to simulated intestinal fluid were used to evaluate the pharmaceutical performance. Subsequently,
the formulations were evaluated in vivo in rats.Whenhigh enough amounts ofHPMCwere co-administered
with itraconazole-loaded SBA-15 (itraconazole:SBA-15:HPMC 1:4:6), the extent of absorption was
increased by more than 60% when compared to SBA-15 without precipitation inhibitors (AUC
14,937 ± 1617 versus 8987 ± 2726 nM h). HPMCAS was found ineffective in enhancing the in vivo performance
of SBA-15 due to its insolubility in the stomach. The results of this study demonstrate that the pharmaceutical
performance of SBA-15 is enhanced through addition of an appropriate precipitation inhibitor.
ISSN: 0939-6411
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Drug Delivery and Disposition
Centre for Surface Chemistry and Catalysis
Physical Metallurgy and Materials Engineering Section (-)
× corresponding author
# (joint) last author

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