Trospium Chloride: Unusual Example of Polymorphism Based on Structure Disorder

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.