American Chemical Society
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Interpreting the Disordered Crystal Structure of Sodium Naproxen Tetrahydrate

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journal contribution
posted on 2013-08-07, 00:00 authored by Andrew D. Bond, Claus Cornett, Flemming H. Larsen, Haiyan Qu, Dhara Raijada, Jukka Rantanen
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.