Formulation Technology Research Laboratories, Daiichi Sankyo Co, Ltd, 1-2-58, Hiromachi, Tokyo 140-8710, Japan.
Int J Pharm. 2010 Jan 4;383(1-2):18-23. doi: 10.1016/j.ijpharm.2009.08.037. Epub 2009 Sep 2.
The purpose of this study was to elaborate the relationship between the (13)C CP/MAS NMR spectra and the recrystallization behavior during the storage of troglitazone solid dispersions. The solid dispersions were prepared by either the solvent method or by co-grinding. The recrystallization behavior under storage conditions at 40 degrees C/94% RH was evaluated by the Kolmogorov-Johnson-Mehl-Avrami (KJMA) equation. Solid dispersions prepared by the solvent method or by prolonged grinding brought about inhibition of the nucleation and the nuclei growth at the same time. No differences in the PXRD profiles were found in the samples prepared by the co-grinding and solvent methods, however, (13)C CP/MAS NMR showed significant differences in the spectra. The correlation coefficients using partial least square regression analysis between the PXRD profiles and the apparent nuclei-growth constant or induction period to nucleation were 0.1305 or 0.6350, respectively. In contrast, those between the (13)C CP/MAS NMR spectra and the constant or the period were 0.9916 or 0.9838, respectively. The (13)C CP/MAS NMR spectra had good correlation with the recrystallization kinetic parameters evaluated by the KJMA equation. Consequently, solid-state NMR was judged to be a useful tool for the prediction of the recrystallization behavior of solid dispersions.
本研究旨在阐述 13C CP/MAS NMR 谱与曲格列酮固体分散体储存过程中重结晶行为之间的关系。固体分散体通过溶剂法或共研磨法制备。在 40°C/94%RH 的储存条件下，通过 Kolmogorov-Johnson-Mehl-Avrami（KJMA）方程评估重结晶行为。溶剂法或长时间研磨制备的固体分散体同时抑制成核和核生长。通过共研磨和溶剂法制备的样品在 PXRD 图谱上没有发现差异，然而，13C CP/MAS NMR 显示出谱图上的显著差异。偏最小二乘回归分析表明，PXRD 图谱与明显的核生长常数或成核诱导期之间的相关系数分别为 0.1305 或 0.6350，而 13C CP/MAS NMR 图谱与常数或周期之间的相关系数分别为 0.9916 或 0.9838。13C CP/MAS NMR 谱与通过 KJMA 方程评估的重结晶动力学参数具有良好的相关性。因此，固态 NMR 被认为是预测固体分散体重结晶行为的有用工具。
