Tuesday, January 5, 2016

Structural characterization of cevimeline and its trans-impurity by single crystal XRD


Single crystal X-ray analysis of cevimeline is reported for the first time.
Single crystal X-ray analysis of trans-cevimeline is reported for the first time.
PXRD, thermal analysis and solubility studies of both compounds is provided.


Cevimeline is muscarinic receptor agonist which increases secretion of exocrine glands. Cevimeline base is a liquid (m.p. 20–25 °C) at ambient conditions, therefore its pharmaceutical formulation as a solid hydrochloride hemihydrate has been developed. The synthesis of cevimeline yields its cis- and trans-isomers and only the cis-isomer is recognized as the API and used in the finished formulation. In this study structural and physicochemical investigations of hydrochloride hemihydrates of cis- and trans-cevimelines have been performed. Single crystal X-ray analyses of both cis- and trans-isomers of cevimeline are reported here for the first time. It was found that the cis-isomer, the API, has less dense crystal packing, lower melting point and higher solubility in comparison to the trans-isomer.

Graphical abstract

Image for unlabelled figure


  • Cevimeline
  • trans-Cevimeline
  • Impurity standard
  • Single crystal X-ray analysis;
  • Thermal analysis
  • Solubility