Structural Characterization of Cevimeline and Its Trans-Impurity by Single Crystal XRD

Journal of Pharmaceutical and Biomedical Analysis 2016
Dmitrijs Stepanovs, Zenta Tetere, Irisa Rāviņa, Viktors Kumpiņš, Daina Zicāne, Ērika Bizdēna, Janis Bogans, Irina Novosjolova, Agnese Ābele, Remo Merijs-Meri, Juris Fotins, Maksims Čerkasovs, Anatolijs Mišņovs, Māris Turks

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 asolid 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.

Atslēgas vārdi
Cevimeline, trans-Cevimeline, Impurity standard, Single crystal, X-ray analysis, Thermal analysis, Solubility
DOI
10.1016/j.jpba.2015.11.006
Hipersaite
http://www.sciencedirect.com/science/article/pii/S0731708515302260

Stepanovs, D., Tetere, Z., Rāviņa, I., Kumpiņš, V., Zicāne, D., Bizdēna, Ē., Bogans, J., Novosjolova, I., Grigaloviča, A., Merijs-Meri, R., Fotins, J., Čerkasovs, M., Mišņovs, A., Turks, M. Structural Characterization of Cevimeline and Its Trans-Impurity by Single Crystal XRD. Journal of Pharmaceutical and Biomedical Analysis, 2016, Vol.118, 404.-409.lpp. ISSN 0731-7085. Pieejams: doi:10.1016/j.jpba.2015.11.006

Publikācijas valoda
English (en)