An acetonitrile-solvated cocrystal of piroxicam and succinic acid with co-existing zwitterionic and non-ionized piroxicam molecules.

Abstract

This work reports a new acetonitrile (ACN)-solvated cocrystal of piroxicam (PRX) and succinic acid (SA), 2C15H13N3O4S·0.5C4H6O4·C2H3N or PRX:SA:ACN (4:1:2), which adopts the triclinic space group P-1. The outcome of crystallization from ACN solution can be controlled by varying only the PRX:SA ratio, with a higher PRX:SA ratio in solution unexpectedly favouring a lower stoichiometric ratio in the solid product. In the new solvate, zwitterionic (Z) and non-ionized (NI) PRX molecules co-exist in the asymmetric unit. In contrast, the nonsolvated PRX-SA cocrystal contains only NI-type PRX molecules. The ACN molecule entrapped in PRX-SA·ACN does not form any hydrogen bonds with the surrounding molecules. In the solvated cocrystal, Z-type molecules form dimers linked by intermolecular N-H...O hydrogen bonds, whereas every pair of NI-type molecules is linked to SA via N-H...O and O-H...N hydrogen bonds. Thermogravimetry and differential scanning calorimetry suggest that thermal desolvation of the solvate sample occurs at 148 °C, and is followed by recrystallization, presumably of a multicomponent PRX-SA structure. Vibrational spectra (IR and Raman spectroscopy) of PRX-SA·ACN and PRX-SA are also used to demonstrate the ability of spectroscopic techniques to distinguish between NI- and Z-type PRX molecules in the solid state. Hence, vibrational spectroscopy can be used to distinguish the PRX-SA cocrystal and its ACN solvate.