Quantification of compaction-induced crystallinity reduction of a pharmaceutical solid using 19F solid-state NMR and powder X-ray diffraction

19F solid-state nuclear magnetic resonance (NMR) was investigated as an analytical technique to quantify the amorphous phase in a fluorine-containing pharmaceutical candidate. The crystallinity of Compound 1 was calculated using two 19F T1 relaxation-based methods. The first method employs both the pure amorphous and the crystalline reference standards while the second method is model independent and utilizes a single standard. The 19F solid-state NMR results were confirmed with powder X-ray diffraction methods. From X-ray diffraction data, two linear calibration curves were obtained from blends of crystalline and amorphous Compound 1: one is based on the total integrated intensity of selected diffraction peaks and the other on the total intensity of the amorphous halo at 2θ positions that have no interference from crystalline diffraction peaks. The crystallinity of Compound 1 after compaction calculated by both 19F solid-state NMR methods was in excellent agreement with the results from the X-ray calibra...