Issue 5, 2009

Dimorphs of a 1 : 1 cocrystal of ethenzamide and saccharin: solid-state grinding methods result in metastable polymorph

Abstract

Two polymorphs of a cocrystal between an analgesic drug, ethenzamide, and saccharin were prepared and structurally characterized by single crystal X-ray diffraction. Both crystal forms are sustained by a carboxamideimide heterosynthon involving two N–H⋯O hydrogen bonds. Remarkably, the metastable Form II was the only product in the grinding experiments, whereas both polymorphs were obtained by solution crystallization. Metastable Form II converts to the stable Form I in slurry experiments and also in the solution. Hot-stage microscopy experiments and sublimation at reduced pressure suggest that heating Forms I and II beyond their melting points leads to dissociation of the cocrystal into its crystalline starting components. This study highlights the importance of multiple screening techniques for cocrystal polymorphs and also sheds light on the ability of the solid-state grinding to produce the metastable polymorph of a cocrystal.

Graphical abstract: Dimorphs of a 1 : 1 cocrystal of ethenzamide and saccharin: solid-state grinding methods result in metastable polymorph

Supplementary files

Article information

Article type
Paper
Submitted
28 nov 2008
Accepted
12 jan 2009
First published
04 feb 2009

CrystEngComm, 2009,11, 889-895

Dimorphs of a 1 : 1 cocrystal of ethenzamide and saccharin: solid-state grinding methods result in metastable polymorph

S. Aitipamula, P. S. Chow and R. B. H. Tan, CrystEngComm, 2009, 11, 889 DOI: 10.1039/B821373A

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