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Aging behavior of pharmaceutical formulations of itraconazole on SBA-15 ordered mesoporous silica carrier material

โœ Scribed by Randy Mellaerts; Kristof Houthoofd; Ken Elen; Hong Chen; Michiel Van Speybroeck; Jan Van Humbeeck; Patrick Augustijns; Jules Mullens; Guy Van den Mooter; Johan A. Martens


Book ID
104057462
Publisher
Elsevier Science
Year
2010
Tongue
English
Weight
449 KB
Volume
130
Category
Article
ISSN
1387-1811

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โœฆ Synopsis


SBA-15 ordered mesoporous material is an excellent carrier material for the poorly soluble drug molecule itraconazole. Immediate itraconazole release is obtained upon contacting the formulation with simulated biological fluid. The stability of the formulation upon storage was investigated. Samples were stored for 3, 6 and 12 months at 4 and 25 ยฐC and relative humidity of 0%, 52% and 97%. The original release behavior was maintained upon storage in dry conditions. Surprisingly, long-term storage at a relative humidity of 52% or 97% had a beneficial effect on the release. The surface chemical modification of the formulation upon storage in humid atmosphere was investigated using nitrogen adsorption, 29 Si MAS NMR, TGA-MS, XPS and DSC. Itraconazole phase analysis using DSC and analysis of the presence of itraconazole concentration gradients using XPS revealed that storage did not cause migration, aggregation nor crystallization of itraconazole. The surface of the pores of SBA-15 was found to undergo hydroxylation at high relative humidity. The enhanced hydrophilicity was responsible for the observed improvement of itraconazole release upon contact with water. These findings contribute to the understanding of drug delivery systems based on mesoporous silica carrier materials.


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