Solid-state NMR (ssNMR) has been increasingly recognized as a high resolution spectroscopic tool to characterize pharmaceutical materials. [Trends in Analytical Chemistry, 135, 116152, 2021] However, ssNMR application in pharmaceutical sciences is often limited by the low sensitivity from the natural abundance and the nature of multiple components. Approximately 30% of pharmaceutical compounds are fluorinated in order to modulate the properties of drug molecules and fluorine is usually absent from polymeric excipients. Moreover, 19F has an inherently high gyromagnetic ratio and high natural abundance. Therefore, 19F magic angle spinning (MAS) NMR is a promising technique in pharmaceutical applications. In the past few years, we have developed and utilized 19F MAS to study a few critical pharmaceutical attributes. These studies include (1) quantifying drug substance stability in pharmaceutical formulations; [Molecular pharmaceutics 16, 825, 2019] (2) investigating molecular mechanism of crystalline-to-amorphous conversion [The Journal of Physical Chemistry B 124, 5271, 2020]; (3) uncover molecular interaction in pharmaceutical formulation; [Molecular pharmaceutics 16, 2579, 2019]; (4) characterizing drug products by designing the first three-dimensional 19F-1H-1H correlation pulse sequence under ultrafast MAS; [Analytical chemistry 91, 6217, 2019] and (5) measuring drug-polymer interaction in amorphous solid dispersions at atomic level; [Molecular pharmaceutics 17, 2585, 2020] In this presentation, we will overview the technical challenges of pharmaceutical analysis and illustrate 19F ssNMR as a powerful tool to characterize drug substances and drug products.
