23Na magic-angle spinning and double-rotation NMR study of solid forms of sodium valproate

Sodium valproate is a pharmaceutical with applications in the treatment of epilepsy, bipolar disorder, and other ailments. Sodium valproate can exist in many hydrated and acid-stabilized forms in the solid state, and it can be difficult to obtain precise structural information about many of these. Here, we present a C-13 and Na-23 solid-state NMR study of several forms of sodium valproate, only one of which has been previously structurally characterized by single-crystal X-ray diffraction. Na-23 magic-angle spinning (MAS), double-rotation (DOR), and multiple-quantum magic-angle spinning (MQMAS) NMR spectra are shown to provide useful information on the number of molecules in the asymmetric unit, the local coordination geometry of the sodium cations, and the presence of amorphous phases. Two previously identified forms are shown to be highly similar, or identical, according to the Na-23 NMR data. The utility of carrying out both DOR and MQMAS NMR experiments to identify all crystallographically unique sites is demonstrated. C-13 cross-polarization MAS NMR spectra also provide complementary information on the number of molecules in the asymmetric unit and the crystallinity of the sample.