A Solid-State NMR Study of Amorphous Ezetimibe Dispersions in Mesoporous Silica
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The purpose of this work is to examine the ability of methods based on multinuclear and multidimensional solid-state NMR (SSNMR) to perform detailed characterization of amorphous dispersions of ezetimibe adsorbed on mesoporous silica.
Ezetimibe was loaded into two types of mesoporous silica with average pore sizes of 2.5 and 21 nm. The mesoporous materials were characterized by powder X-ray diffraction (PXRD), vibrational spectroscopy, differential scanning calorimetry, and 1H, 13C, 19F, and 29Si SSNMR analysis including relaxation time measurements. Interactions between the drug and silica were investigated using 1D and 2D SSNMR methods based on dipolar correlation using cross-polarization (CP) and spin diffusion.
PXRD was used to show the absence of crystalline ezetimibe in the mesoporous materials, and 19F SSNMR was used to assess drug physical state and study mobility. 19F-29Si CP methods were used to directly detect adsorbed ezetimibe. 1H-13C, 1H-19F, and 1H-29Si, and heteronuclear correlation and 1H homonuclear correlation experiments were used to investigate interactions between the drug and silica through 1H environments.
SSNMR methods were able to detect interactions between the drug and the silica substrate. Differences between the drug loaded onto silica with two different pore sizes were observed, including differences in hydrogen bonding environment and molecular mobility. These methods should be useful for characterization of similar systems.
KEY WORDSamorphous dispersion dipolar correlation mesoporous silica powder X-ray diffraction solid-state NMR
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