title: Influence of the solid form of siramesine hydrochloride on its behavior in aqueous environments.
abstract: OBJECTIVE
  To study the influence of solid form on the behavior of the salt siramesine hydrochloride in aqueous environments.
  
  
  METHODS
  The solubilities and dissolution rates of siramesine hydrochloride anhydrate and monohydrate were determined at pH 3.4 and 6.4, and precipitates were examined by X-ray powder diffraction. The mechanism of anhydrate-hydrate conversion was investigated by optical microscopy, and wet massing of the anhydrate was carried out using water and 60% (v/v) ethanol separately as granulation liquids. The wet masses were analyzed using Raman microscopy.
  
  
  RESULTS
  At pH 3.4 the anhydrate and monohydrate salts exhibited similar dissolution profiles. At pH 6.4 both the anhydrate and monohydrate salts formed supersaturated solutions of high apparent solubility. From the anhydrate solution, precipitation of the free base occurred, while the solution of the monohydrate salt remained in the supersaturated state. This resulted in a superior dissolution profile of the monohydrate salt. Microscopy and wet massing experiments showed that the anhydrate-hydrate conversion of siramesine hydrochloride was solution-mediated and dissolution-controlled.
  
  
  CONCLUSIONS
  During development of a formulation based on the anhydrate salt, the risk of processing-induced transformation to the monohydrate form as well as precipitation of the free base should be considered.
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
authors.initials: H
authors.lastname: Lopez de Diego
authors.forename: Michiel
authors.initials: M
authors.lastname: Ringkjøbing Elema
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
authors.forename: Anette
authors.initials: A
authors.lastname: Müllertz
authors.forename: Lars
authors.initials: L
authors.lastname: Hovgaard
mesh_terms: D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D004304:Dosage Forms; D000431:Ethanol / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000737:chemistry*; D007700:Kinetics; D008853:Microscopy; D044367:Phase Transition; D033362:Powder Diffraction; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013059:Spectrum Analysis, Raman; D013141:Spiro Compounds / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry*
chemical_list: D004304:Dosage Forms; D007211:Indoles; C109644:Lu 28-179; D012997:Solvents; D013141:Spiro Compounds; D014867:Water; D000431:Ethanol