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.