Characterization of three crystalline forms (VIII, XI, and XII) and the amorphous form (V) of delavirdine mesylate using 13C CP/MAS NMR.

PURPOSE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.