Tofogliflozin Salt Cocrystals with Sodium Acetate and Potassium Acetate

Chem Pharm Bull (Tokyo). 2018;66(11):1035-1040. doi: 10.1248/cpb.c18-00483.

Abstract

We investigated the salt cocrystals formed by tofogliflozin with sodium acetate and potassium acetate by determining the crystal structures of the salt cocrystals and characterizing the solid states. The salt cocrystal screening using the slurry method and the liquid-assisted grinding method resulted in the formation of tofogliflozin-sodium acetate 1 : 1 and tofogliflozin-potassium acetate 1 : 1 salt cocrystals. Single-crystal X-ray diffraction revealed that, although each salt cocrystal belongs to a different space group, both of the salt cocrystals have almost similar structural features, including the conformation of tofogliflozin molecules, the coordination to Na+/K+ ions, and hydrogen bonds. The salt cocrystals exhibited extreme hygroscopicity with deliquescence, which is also a property of sodium acetate and potassium acetate. In addition, tofogliflozin-potassium acetate salt cocrystal had two polymorphs, which were enantiotropically related.

Keywords: enantiotropy; hygroscopicity; polymorph; salt cocrystal; tofogliflozin.

MeSH terms

  • Benzhydryl Compounds / chemistry*
  • Crystallography, X-Ray
  • Glucosides / chemistry*
  • Models, Molecular
  • Molecular Conformation
  • Potassium Acetate / chemistry*
  • Salts / chemistry
  • Sodium Acetate / chemistry*

Substances

  • Benzhydryl Compounds
  • Glucosides
  • Salts
  • Sodium Acetate
  • Potassium Acetate
  • 6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol