Solid–Solid Transition between Hydrated Racemic Compound and Anhydrous Conglomerate in Na-Ibuprofen: A Combined X‑ray Diffraction, Solid-State NMR, Calorimetric, and Computational Study

A combined X-ray diffraction (XRD),
solid state nuclear magnetic
resonance (SSNMR), differential scanning calorimetry (DSC), and modeling
approach has been applied to study the solid–solid transition
of ibuprofen sodium salt between the hydrated racemic compound (RS-H)
and the anhydrous conglomerate (RS-A). For comparison, the dihydrate
→ anhydrous transformation of the sodium salt of the pure S-enantiomer
of ibuprofen was also investigated by means of SSNMR and DSC. All
the solid state studies indicate that the RS-H → RS-A transition
is fully reversible under different experimental conditions [temperature,
pressure (ambient and vacuum), and type of atmosphere (N2, air, and static dry by P2O5)]. The static
and dynamic disorder affecting the isobutyl fragment in RS-H, already
observed by SSNMR, has been further investigated by single crystal
XRD and computational techniques. On these grounds, a model for the
dihydrate → anhydrous solid–solid transformations is
proposed.