Title: Itraconazole/TPGS/Aerosil (R) 200 solid dispersions Characterization, physical stability and in vivo performance
Authors: Van Eerdenbrugh, Bernard ×
Van Speybroeck, Michiel
Mols, Rafaƫl
Houthoofd, Kristof
Martens, Johan
Froyen, Ludo
Van Humbeeck, Jan
Augustijns, Patrick
Van den Mooter, Guy #
Issue Date: Oct-2009
Publisher: Elsevier
Series Title: European Journal of Pharmaceutical Sciences vol:38 issue:3 pages:270-278
Abstract: Solid dispersions were successfully prepared by co-spray-drying of TPGS-stabilized itraconazole nanosuspensions with Aerosil (R) 200, followed by heat treatment of the powders. The itraconazole/Aerosil (R) 200 weight ratios amounted to 50/50, 30/70, 40/60 and 20/80. The itraconazole content of the powders was close to the expected value, with relative errors between 0.3% and 7.8%. X-ray powder diffraction (XRPD), solid state NMR (SSNMR) and differential scanning calorimetry (DSC) evaluation on the powders revealed the formation of amorphous itraconazole and the absence of glassy itraconazole. Dissolution of the powders was enhanced compared to crystalline and glassy itraconazole (a 2-dimensional structured form of itraconazole). However, no clear trend could be observed between drug loading and dissolution performance of the solid dispersions. Upon storage, conversion to crystalline itraconazole was observed for the 50/50 powder based on XRPD, SSNMR and DSC measurements. Although the 40/60 powder remained X-ray amorphous upon storage. DSC did reveal that a small fraction (7.5 +/- 1.6% after 10 months of storage) of itraconazole crystallized upon storage. For the 30/70 and 20/80 dispersions, no crystallization could be seen. After 10 months of storage, important changes in the dissolution behavior of the powders were observed. A decrease in dissolution performance was seen for the 50/50 dispersion, which could be attributed to the crystallization of itraconazole. On the other hand, the 40/60,30/70 and 20/80 dispersions showed an increase in dissolution rate (more than 60% after 10 min). Although not completely clear at this stage, adsorption of itraconazole onto the Aerosil (R) 200 surface during storage might be responsible for this behavior. Finally, in vivo experiments were performed in the rat. Oral bioavailability of the 30/70 dispersion was, although lower compared to the marketed Sporanox (R) formulation, significantly enhanced compared to the crystalline drug. (C) 2009 Elsevier B.V. All rights reserved.
ISSN: 0928-0987
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Centre for Surface Chemistry and Catalysis
Physical Metallurgy and Materials Engineering Section (-)
Drug Delivery and Disposition
× corresponding author
# (joint) last author

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