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.