Three-Dimensional NMR Spectroscopy of Fluorinated Pharmaceutical Solids under Ultrafast Magic Angle Spinning

High-resolution solid-state analysis of multicomponent molecular systems, e.g., pharmaceutical formulations, is a great challenge. Solid-state NMR (ssNMR) plays a critical role in the characterization of solid dosage forms due to its capabilities of chemical identification, quantification, and structural elucidation at a molecular level. However, the low NMR sensitivity as well as the high spectral complexity and low drug loading of multicomponent products hinder an in-depth investigation of the active pharmaceutical ingredient (API) at the natural isotopic abundance. Herein, we developed two new three-dimensional (3D) ssNMR methods, including 1H-19F-1H and 19F-19F-1H correlations, and successfully applied them to characterize a fluorinated drug molecule, aprepitant, and its commercial nanoparticulate formulation EMEND® (Merck & Co, Inc, Kenilworth, NJ, USA). These 1H-detection methods utilize the significantly enhanced sensitivity and resolution of 1H and 19F afforded by 60 kHz ultrafast magic angle spin...