19F solid-state NMR spectroscopic investigation of crystalline and amorphous forms of a selective muscarinic M3 receptor antagonist, in both bulk and pharmaceutical dosage form samples

The purpose of the following investigation was to display the utility of F-19 solid-state nuclear magnetic resonance (NMR) in both distinguishing between solid forms of a selective muscarinic M-3 receptor antagonist and characterizing the active pharmaceutical ingredient in low-dose tablets. Ambient- and elevated-temperature solid-state F-19 fast (15 kHz) magic-angle spinning (MAS) NMR experiments were employed to obtain desired spectral resolution in this system. Ambient sample temperature combined with rotor frequencies of 15 kHz provided adequate F-19 peak resolution to successfully distinguish crystalline and amorphous forms in this system. Additionally, elevated-temperature F-19 MAS NMR further characterized solid forms through F-19 resonance narrowing brought about by the phenomenon of solvent escape. Similar solvent dynamics at elevated temperatures were utilized in combination with ambient-temperature F-19 MAS NMR analysis to provide excipient-free spectra to unambiguously identify the active pharmaceutical ingredient (API) conversion from crystalline Form I to the amorphous form in low-dose tablets. It is shown that F-19 solid-state NMR is exceptionally powerful in distinguishing amorphous and crystalline forms in both bulk and formulation samples.