Quantification of compaction-induced crystallinity reduction of a pharmaceutical solid using 19F solid-state NMR and powder X-ray diffraction.
(19)F 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 (19)F T(1) 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 (19)F 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 2theta positions that have no interference from crystalline diffraction peaks. The crystallinity of Compound 1 after compaction calculated by both (19)F solid-state NMR methods was in excellent agreement with the results from the X-ray calibration curves. (19)F solid-state NMR was shown to be a powerful technique in determining the amount of amorphous phase present in a pharmaceutical solid.
Liu
Jodi
J
Small Molecule Pharmaceutical R&D, Amgen Inc., Thousand Oaks, CA 91320, USA.
Nagapudi
Karthik
K
Kiang
Y-H
YH
Martinez
Ezequiel
E
Jona
Janan
J
D003460:Crystallization; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods; D014961:X-Ray Diffraction / Q000379:methods*
D004364:Pharmaceutical Preparations