TY - JOUR

T1 - An acetonitrile-solvated cocrystal of piroxicam and succinic acid with co-existing zwitterionic and non-ionized piroxicam molecules

AU - Liu, Xiaojiao

AU - Michalchuk, Adam A.L.

AU - Pulham, Colin R.

AU - Boldyreva, Elena V.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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. 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.

AB - 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. 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.

KW - cocrystal

KW - crystal structure

KW - piroxicam

KW - solvate

KW - succinic acid

KW - DRUG

KW - CRYSTALLIZATION

KW - BETA-CYCLODEXTRIN

KW - CRYSTALS

UR - http://www.scopus.com/inward/record.url?scp=85058039915&partnerID=8YFLogxK

U2 - 10.1107/S2053229618016911

DO - 10.1107/S2053229618016911

M3 - Article

C2 - 30601128

AN - SCOPUS:85058039915

VL - 75

SP - 29

EP - 37

JO - Acta Crystallographica Section C: Structural Chemistry

JF - Acta Crystallographica Section C: Structural Chemistry

SN - 2053-2296

IS - 1

ER -