Relationships between Anhydrous and Solvated Species of Dexketoprofen Trometamol: A Solid-State Point of View

The three different solid forms of dexktoprofen trometamol (DK-T_A, DK-T_B, and DK-T_2H2O) have been studied by using X-ray diffraction and calorimetric methods. In the molecular and crystal structure of DK-T_A, the thermodynamically stable form used in the tablets production process, all the potential H-bond donors and acceptors of each trometamol cation are involved in strong H- bonds which hold together the cations as well as the dexketoprofen/trometamol ionic pairs. The dihydrate species is quickly formed starting from DK-T_A apparently without the formation of an amorphous phase, and the process is fully reversible. In addition, the two solids have comparable crystal density (cell parameters and space group of the resulting hydrate were determined by X-ray powder diffraction). We speculate that the anhydrous and hydrate crystal architectures did not suffer upon the hydration/dehydration process and that the hydrate form belongs to the class of the channel hydrates and most probably is a planar hydrate. Finally, the unit cell parameters and space group were determined also for the metastable DK-T_B solid form.