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[资源] Preparation, structural analysis, and properties of tenoxicam cocrystals

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Preparation, structural analysis, and properties of tenoxicam cocrystals
Jagdishwar R. Patela,c, Robert A. Q1 Carltonb, Thomas E. Needhamc, Clinton O. Chichesterc,
Frederick G. Vogtb,

a b s t r a c t
Cocrystals of tenoxicam, a non-steroidal anti-inflammatory drug, are screened, prepared, and characterized
in this study. Nine tenoxicam cocrystals were identified using solvent-drop grinding (SDG)
techniques. Structural characterization was performed using powder X-ray diffraction (PXRD), differential
scanning calorimetry, and multinuclear solid-state NMR (SSNMR). Thermal analysis, PXRD, and 1D
SSNMR are used to detect solvates and phase mixtures encountered in SDG cocrystal screening. 2D SSNMR
methods are then used to confirm cocrystal formation and determine structural aspects for selected
cocrystals formed with saccharin, salicylic acid, succinic acid, and glycolic acid in comparison to Forms I
and III of tenoxicam. Molecular association is demonstrated using cross-polarization heteronuclear dipolar
correlation (CP-HETCOR) methods involving 1H and 13C nuclei. Short-range 1H–13C CP-HETCOR and
1H–1H double-quantum interactions between atoms of interest, including those engaged in hydrogen
bonding, are used to reveal local aspects of the cocrystal structure. 15N SSNMR is used to assess ionization
state and the potential for zwitterionization in the selected cocrystals. The tenoxicam saccharin
cocrystal was found to be similar in structure to a previously-reported cocrystal of piroxicam and saccharin.
The four selected cocrystals yielded intrinsic dissolution rates that were similar or reduced relative
to tenoxicam Form III.
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