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.