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

Abstract

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 (N 2 , air, and static dry by P 2 O 5 )]. 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.

Improving the granule strength of roller-compacted ibuprofen sodium for hot-melt coating processing

“…From a thermodynamic point of view, these observations explain why only the hydrated form of ibuprofen sodium is found after the roller compaction process. Additionally, the full reversal of transition from anhydrate to dihydrate of ibuprofen sodium was reported to be almost completed after about one hour in the air at room temperature (Rossi et al, 2014), which is in agreement with our results.…”

Transformation of acidic poorly water soluble drugs into ionic liquids

“…This pattern followed the general trend that amorphous solids or liquids adsorb water within their bulk and their surfaces, in contrast to crystalline forms in which water adsorption is restricted to the crystal surfaces [28]. However, crystalline sodium salts of carboxylic acids displayed high values of water sorption, particularly for Diclofenac and Ketoprofen sodium salts which were even more hygroscopic than the TBP salts and transformed into tetrahydrates and Ibuprofen sodium into a dihydrate as reported before [29][30][31]. Sulfonamide sodium salts were only slightly hygroscopic and did not form hydrates.…”

The solid-state structure of the β-blocker metoprolol: a combined experimental and in silico investigation

“…Secondly, there is a great deal of interest by the pharmaceutical industry in the investigation of solids containing APIs with improved physicochemical properties. In this context, the assessment of the phase stability and of the thermal behaviour of compounds of pharmaceutical interest (such as temperature-related phase transformations, anisotropic lattice expansion/contraction and thermal stability) provide valuable information (Rossi et al, 2014;Paoli et al, 2016). For example, powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) have been used to characterize time-controlled metoprolol tartrate delivery systems using acrylic resins (Eudragit RL and Eudragit RS) for the coating.…”