title: Structural characterization of cevimeline and its trans-impurity by single crystal XRD.
abstract: 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.
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV-1006, Latvia; Faculty of Materials Science and Applied Chemistry, Riga Technical University, P. Valdena 3, Riga LV-1048, Latvia.
authors.forename: Dmitrijs
authors.initials: D
authors.lastname: Stepanovs
authors.affiliation: Faculty of Materials Science and Applied Chemistry, Riga Technical University, P. Valdena 3, Riga LV-1048, Latvia.
authors.forename: Zenta
authors.initials: Z
authors.lastname: Tetere
authors.affiliation: Faculty of Materials Science and Applied Chemistry, Riga Technical University, P. Valdena 3, Riga LV-1048, Latvia.
authors.forename: Irisa
authors.initials: I
authors.lastname: Rāviņa
authors.affiliation: Faculty of Materials Science and Applied Chemistry, Riga Technical University, P. Valdena 3, Riga LV-1048, Latvia.
authors.forename: Viktors
authors.initials: V
authors.lastname: Kumpiņš
authors.affiliation: Faculty of Materials Science and Applied Chemistry, Riga Technical University, P. Valdena 3, Riga LV-1048, Latvia.
authors.forename: Daina
authors.initials: D
authors.lastname: Zicāne
authors.affiliation: Faculty of Materials Science and Applied Chemistry, Riga Technical University, P. Valdena 3, Riga LV-1048, Latvia.
authors.forename: Ērika
authors.initials: Ē
authors.lastname: Bizdēna
authors.affiliation: Latvian Biomedical Research and Study Centre, Ratsupites 1, Riga LV-1067, Latvia.
authors.forename: Jānis
authors.initials: J
authors.lastname: Bogans
authors.affiliation: Faculty of Materials Science and Applied Chemistry, Riga Technical University, P. Valdena 3, Riga LV-1048, Latvia.
authors.forename: Irina
authors.initials: I
authors.lastname: Novosjolova
authors.affiliation: Faculty of Materials Science and Applied Chemistry, Riga Technical University, P. Valdena 3, Riga LV-1048, Latvia.
authors.forename: Agnese
authors.initials: A
authors.lastname: Grigaloviča
authors.affiliation: Faculty of Materials Science and Applied Chemistry, Riga Technical University, P. Valdena 3, Riga LV-1048, Latvia.
authors.forename: Remo Merijs
authors.initials: RM
authors.lastname: Meri
authors.affiliation: Pharma and Chemistry Competence Centre of Latvia, Aizkraukles 21, Riga LV-1006, Latvia.
authors.forename: Juris
authors.initials: J
authors.lastname: Fotins
authors.affiliation: Pharma and Chemistry Competence Centre of Latvia, Aizkraukles 21, Riga LV-1006, Latvia.
authors.forename: Maksims
authors.initials: M
authors.lastname: Čerkasovs
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV-1006, Latvia; Faculty of Materials Science and Applied Chemistry, Riga Technical University, P. Valdena 3, Riga LV-1048, Latvia.
authors.forename: Anatoly
authors.initials: A
authors.lastname: Mishnev
authors.affiliation: Faculty of Materials Science and Applied Chemistry, Riga Technical University, P. Valdena 3, Riga LV-1048, Latvia. Electronic address: maris_turks@ktf.rtu.lv.
authors.forename: Māris
authors.initials: M
authors.lastname: Turks
mesh_terms: D018360:Crystallography, X-Ray / Q000379:methods; D004340:Drug Contamination; D018721:Muscarinic Agonists / Q000032:analysis / Q000737:chemistry; D011812:Quinuclidines / Q000032:analysis* / Q000737:chemistry*; D013237:Stereoisomerism; D013876:Thiophenes / Q000032:analysis* / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods*
chemical_list: D018721:Muscarinic Agonists; D011812:Quinuclidines; D013876:Thiophenes; C059240:cevimeline
keywords: Cevimeline; Impurity standard; Single crystal X-ray analysis; Solubility; Thermal analysis; trans-Cevimeline