title: Structural characterisation and dehydration behaviour of siramesine hydrochloride.
abstract: In this study the crystal structures of siramesine hydrochloride anhydrate alpha-form and siramesine hydrochloride monohydrate were determined, and this structural information was used to explain the physicochemical properties of the two solid forms. In the crystal structure of the monohydrate, each water molecule is hydrogen bonded to two chloride ions, and thus the water is relatively strongly bound in the crystal. No apparent channels for dehydration were observed in the monohydrate structure, which could allow transmission of structural information during dehydration. Instead destructive dehydration occurred, where the elimination of water from the monohydrate resulted in the formation of an oily phase, which subsequently recrystallised into one or more crystalline forms. Solubility and intrinsic dissolution rate of the anhydrate alpha-form and the monohydrate in aqueous media were investigated and both were found to be lower for the monohydrate compared to the anhydrate alpha-form. Finally, the interactions between water molecules and chloride ions in the monohydrate as well as changes in packing induced by water incorporation could be detected by spectroscopic techniques.
authors.affiliation: Faculty of Pharmaceutical Sciences, Department of Pharmaceutics and Analytical Chemistry, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark. anz@farma.ku.dk
authors.forename: Anne
authors.initials: A
authors.lastname: Zimmermann
authors.forename: Fang
authors.initials: F
authors.lastname: Tian
authors.forename: Heidi Lopez
authors.initials: HL
authors.lastname: de Diego
authors.forename: Karla
authors.initials: K
authors.lastname: Frydenvang
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
authors.forename: Michiel Ringkjøbing
authors.initials: MR
authors.lastname: Elema
authors.forename: Lars
authors.initials: L
authors.lastname: Hovgaard
mesh_terms: D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D003890:Desiccation; D006358:Hot Temperature; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D007211:Indoles / Q000737:chemistry*; D008958:Models, Molecular; D012995:Solubility; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D019265:Spectroscopy, Near-Infrared; D013059:Spectrum Analysis, Raman; D013141:Spiro Compounds / Q000737:chemistry*; D013818:Thermogravimetry; D014961:X-Ray Diffraction
chemical_list: D007211:Indoles; C109644:Lu 28-179; D013141:Spiro Compounds