Relevance of the theoretical critical pore radius in mesoporous silica for fast crystallizing drugs

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26.10.2020
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01A - Journal article
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International Journal of Pharmaceutics
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591
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Elsevier
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Abstract
Formulation of poorly water-soluble drugs with mesoporous silica has become a thriving field of pharmaceutics. The theoretical critical pore diameter has been introduced as a maximum value below which an undesired drug crystallization is suppressed by spatial confinement. Currently, only few values have been reported and study of fast crystallising drugs is missing especially at relevant storage temperatures. This study investigated the critical pore diameter of three model drugs with a poor glass-forming ability (i.e. haloperidol, carbamazepine and benzamide) using different mesoporous carriers (Parteck® SLC 500, Neusilin® US2, Syloid® XDP 3050 and Aeroperl® 300 Pharma) and subsequently monitored physical formulation stability over three months by X-ray powder diffraction. The selected drugs showed clear differences in their estimated critical pore diameters, whereas a temperature dependence was barely relevant for pharmaceutical storage conditions. Superior stability was noted for the formulations containing benzamide in line with its predicted relatively large critical pore diameter of 29.5 nm. Contrarily, impaired physical stability depending on drug loading was observed in the case of haloperidol representing a compound with a rather small critical pore diameter (8.4 nm). These findings confirm the importance of estimating the critical pore diameter, especially for poor glass-forming drugs.
Keywords
Critical pore diameter, Mesoporous silica, Amorphous, Glass forming ability, Drug loading, physical stability
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0378-5173
1873-3476
Language
English
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Yes
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Published
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Citation
VRANÍKOVÁ, Barbora, Andreas NIEDERQUELL und Martin KUENTZ, 2020. Relevance of the theoretical critical pore radius in mesoporous silica for fast crystallizing drugs. International Journal of Pharmaceutics. 26 Oktober 2020. Bd. 591. DOI 10.1016/j.ijpharm.2020.120019. Verfügbar unter: https://irf.fhnw.ch/handle/11654/32424