Gao P
Pharmaceutical Development, Pharmacia & Upjohn, Kalamazoo, Michigan 49001, USA.
Pharm Res. 1998 Sep;15(9):1425-33. doi: 10.1023/a:1011909907031.
The application of solid-state nuclear magnetic resonance (NMR) characterization of three crystalline forms (VIII, XI, XII) and the amorphous form V of delavirdine mesylate (DLV-M) is presented.
Conventional 13CCP (cross-polarization)/MAS (magic angle spinning) NMR and related spectral editing methods were employed. NMR relaxation times (T1pH, T1H, and T1C) were also measured.
Distinctly different spectral features among the four solid forms were observed, indicating high sensitivity of 13C NMR to the variations in solid structure. Assessment based on NMR data suggests that both anhydrous forms VIII and XI may contain one molecule per asymmetric unit. DLV may adopt a similar molecular conformation in the two forms. In contrast, form XII is found to consist of two molecules per asymmetric unit. Molecule conformation of DLV in forms VIII, XI, and XII is altered from the dominant conformer in solution. The amorphous form V may contain DLV molecules of a variety of conformations. NMR relaxation times (T1PH, T1H, and T1C) provide valuable information about the motional characteristics in these solids. Values and the rank order of T1pH, T1H, and T1C also reveal significant differences in local environments and the short range order among the four forms.
Four solid forms of DLV-M (V, VIII, XI, and XII) can be distinctly differentiated by 13C CP/MAS NMR spectroscopy and their structural difference can be partially revealed without obtaining single crystal data. NMR relaxation times reveal motion dynamics and aid structural elucidation for these forms.
介绍了对甲磺酸地拉韦啶（DLV-M）的三种晶型（VIII、XI、XII）和无定形V型进行固态核磁共振（NMR）表征的应用。
采用常规的13C CP（交叉极化）/MAS（魔角旋转）NMR及相关光谱编辑方法。还测量了NMR弛豫时间（T1pH、T1H和T1C）。
观察到四种固态形式之间存在明显不同的光谱特征，表明13C NMR对固体结构变化具有高灵敏度。基于NMR数据的评估表明，无水晶型VIII和XI可能每个不对称单元包含一个分子。DLV在这两种晶型中可能采用相似的分子构象。相比之下，发现晶型XII每个不对称单元由两个分子组成。DLV在晶型VIII、XI和XII中的分子构象与溶液中的主要构象不同。无定形V型可能包含多种构象的DLV分子。NMR弛豫时间（T1PH、T1H和T1C）提供了有关这些固体中运动特征的有价值信息。T1pH、T1H和T1C的值及其排序也揭示了四种晶型在局部环境和短程有序方面的显著差异。
通过13C CP/MAS NMR光谱可以明显区分DLV-M的四种固态形式（V、VIII、XI和XII），并且无需获得单晶数据即可部分揭示它们结构上的差异。NMR弛豫时间揭示了这些晶型的运动动力学并有助于结构解析。
