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Physical State of Poorly Water Soluble Therapeutic Molecules Loaded into SBA-15 Ordered Mesoporous Silica Carriers: A Case Study with Itraconazole and Ibuprofen
Abstract
The ordered mesoporous silica material SBA-15 was loaded with the model drugs itraconazole and ibuprofen using three different procedures: (i) adsorption from solution, (ii) incipient wetness impregnation, and (iii) heating of a mixture of drug and SBA-15 powder. The location of the drug molecules in the SBA-15 particles and molecular interactions were investigated using nitrogen adsorption, TGA, DSC, DRS UV-vis, and XPS. The in vitro release of hydrophobic model drugs was evaluated in an aqueous environment simulating gastric fluid. The effectiveness of the loading method was found to be strongly compound dependent. Incipient wetness impregnation using a concentrated itraconazole solution in dichloromethane followed by solvent evaporation was most efficient for dispersing itraconazole in SBA-15. The itraconazole molecules were located on the mesopore walls and inside micropores of the mesopore walls. When SBA-15 was loaded by slurrying it in a diluted itraconazole solution from which the solvent was evaporated, the itraconazole molecules ended up in the mesopores that they plugged locally. At a loading of 30 wt %, itraconazole exhibited intermolecular interactions inside the mesopores revealed by UV spectroscopy and endothermic events traced with DSC. The physical mixing of itraconazole and SBA-15 powder followed by heating above the itraconazole melting temperature resulted in formulations in which glassy itraconazole particles were deposited externally on the SBA-15 particles. Loading with ibuprofen was successful with each of the three loading procedures. Ibuprofen preferably is positioned inside the micropores. In vitro release experiments showed fast release kinetics provided the drug molecules were evenly deposited over the mesoporous surface.
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Metadata
- Authors
- Mellaerts, R., Jammaer, J. A. G., Van Speybroeck, M., Chen, H., Humbeeck, J. V., Augustijns, P., Van den Mooter, G., & Martens, J. A.
- Venue
- Langmuir
- Publisher
- American Chemical Society (ACS)
- Published
- 2008-07-17
- Volume
- 24
- Issue
- 16
- Pages
- 8651-8659
- ISSN
- 0743-7463 (ISSN-L)
- 1520-5827
- OpenAlex
- W1997674180
- Cited by
- 259
- References
- 28
- FWCI
- 6.90
- Type
- journal article
- Language
- en
- Open access
- closed
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