Characterization of the structural and dynamic properties of two polymorphs of leflunomide by solid-state NMR

Solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy is a powerful tool for the structural and dynamic characterization of polymorphs, whose pharmaceutical properties can differ in terms of solubility, stability, and bioavailability. In this study, we present the first ssNMR characterization of the two polymorphs α and β of leflunomide, a Disease Modifying Anti-Rheumatic Drug. A multinuclear (1H, 19F, 13C, 15N) NMR approach using spectral and relaxation data confirmed distinct structural and dynamic differences between the two polymorphs. In particular, the reorientational motions of the methyl, phenyl, and trifluoromethyl groups are at least two orders of magnitude faster in the β form.