Trospium Chloride: Unusual Example of Polymorphism Based on Structure Disorder

Abstract

The characterization of the solid state properties of an active pharmaceutical ingredient is a necessary step in drug development. One such API is trospium chloride, an anticholinergic drug used to treat incontinence and overactive bladder syndrome. One crystal form is known but, from the crystallographic point of view, has only been described by the X-ray powder diffraction pattern. Because, to the best of our knowledge, no crystal structures of trospium chloride have been published, we decided to prepare and describe different crystal forms. Using single-crystal X-ray diffraction, the structures of two new polymorphs and of one unstable solvate were solved. All forms were obtained from ethanol mother liquor. Both polymorphs exhibited a significant pseudosymmetrical disorder. The polymorphs were highly similar but were distinguished by their symmetry and the resulting single-crystal diffraction behavior. A detailed inspection of the molecular packing revealed that variations in the short-range disorder most likely gave rise to these two sibling polymorphs, which are hard to distinguish by X-ray powder diffraction.