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

Xiaojiao Liu, Adam A. L. Michalchuk, Colin R. Pulham, Elena V. Boldyreva

Research output: Contribution to journalArticlepeer-review

Abstract

This work reports a new acetonitrile (ACN)-solvated cocrystal of piroxicam (PRX) and succinic acid (SA), 2C(15)H(13)N(3)O(4)S center dot 0.5C(4)H(6)O(4)center dot C2H3N or PRX:SA:ACN (4:1:2), which adopts the triclinic space group P (1) over bar. 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 center dot 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 center dot center dot center dot O hydrogen bonds, whereas every pair of NI-type molecules is linked to SA via N-H center dot center dot center dot O and O-H center dot center dot center dot N hydrogen bonds. Thermogravimetry and differential scanning calorimetry suggest that thermal desolvation of the solvate sample occurs at 148 degrees C, and is followed by recrystallization, presumably of a multicomponent PRX-SA structure. Vibrational spectra (IR and Raman spectroscopy) of PRX-SA center dot 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.

Original languageEnglish
Pages (from-to)29-37
Number of pages16
JournalActa Crystallographica Section C: Structural Chemistry
Volume75
DOIs
Publication statusPublished - 1 Jan 2019

Keywords / Materials (for Non-textual outputs)

  • piroxicam
  • succinic acid
  • crystal structure
  • cocrystal
  • solvate
  • BETA-CYCLODEXTRIN
  • DRUG
  • CRYSTALLIZATION
  • CRYSTALS

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