Structural Characterisation and Dehydration Behaviour of Siramesine Hydrochloride

In this study the crystal structures of siramesine hydrochloride anhydrate α-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 α-form and the monohydrate in aqueous media were investigated and both were found to be lower for the monohydrate compared to the anhydrate α-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. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3596-3607, 2009