An acetonitrile‐solvated cocrystal of piroxicam and succinic acid with co‐existing zwitterionic and non‐ionized piroxicam molecules. Issue 1 (5th December 2018)

• Record Type: Journal Article
• Authors: Liu, Xiaojiao; Michalchuk, Adam A. L.; Pulham, Colin R.; Boldyreva, Elena V.
• Is Part Of: Acta crystallographica. Volume 75:Issue 1(2019)
• Page Start: 29
• Page End: 37
• Publication Date: 2018-12-05
• Subjects: piroxicam -- succinic acid -- crystal structure -- cocrystal -- solvate; Crystallography -- Periodicals; Crystals -- Periodicals; 548.3
• DOI: 10.1107/S2053229618016911
• Languages: English
• ISSNs: 2053-2296

Abstract

Abstract : This work reports a new acetonitrile‐solvated cocrystal of piroxicam (PRX) and succinic acid (SA). The outcome of crystallization from acetonitrile 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. Abstract : This work reports a new acetonitrile (ACN)‐solvated cocrystal of piroxicam (PRX) and succinic acid (SA), 2C15 H13 N3 O4 S·0.5C4 H6 O4 ·C2 H3 N or PRX:SA:ACN (4:1:2), which adopts the triclinic space group P . 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.