Interpreting the Disordered Crystal Structure of Sodium Naproxen Tetrahydrate

The crystal structure of the tetrahydrate of the active pharmaceutical ingredient sodium naproxen is examined using single-crystal X-ray diffraction, supported by 13C and 23Na solid-state NMR. The structure has previously been reported to be a heminonahydrate, Na+(naproxen–)·4.5H2O. The average structure in space group C2 contains layers of naproxen molecules that are ordered, except for two orientations of the carboxyl groups, and Na+/H2O regions that exhibit complex disorder. The atomic positions in the disordered regions are interpreted as Na­(H2O)6 octahedra, alternately sharing edges and faces to define 1-D coordination polymers with translational periodicity twice that of the b axis in the average C2 structure. There is also one noncoordinated H2O molecule per two naproxen molecules, giving an overall formula of {Na2(H2O)7}2+(naproxen–)2(H2O). Two resonances seen for the naproxen methyl group in 13C CP/MAS SS-NMR are accounted for by the presence of two orientations along the doubled b axis for the carboxyl group. A single resonance in the 23Na SS-NMR is consistent with local 21/m symmetry in the Na+/H2O regions. The single-crystal X-ray diffraction pattern contains diffuse rods in positions consistent with the doubled b axis, indicating a disordered stacking sequence for the Na+/H2O sections.