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A multi-technique approach to the study of structural stability and desolvation of two unusual channel hydrate solvates of finasteride

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Abstract

The dehydration/desolvation of two hydrate solvates of the pharmaceutically important compound finasteride (namely, bisfinasteride monohydrate monotetrahydrofuran and bisfinasteride monohydrate mono-1,4-dioxane) has been studied by solid-state nuclear magnetic resonance, powder X-ray diffraction, thermogravimetric analysis (including coupling with mass spectrometry) and dynamic vapour sorption. The structure is unusual in that water holds the host finasteride molecules together by hydrogen bonding to form channels in which the solvent is sited. Whilst the solvent guest molecules are not strongly bound to the host, their presence is essential for structural stability. Desolvation is not found to occur at a well-defined temperature or even to consistently produce the same anhydrous form (form I vs. form II), but is instead highly dependent on the physical environment and, therefore, on the technique used. This behaviour complicates investigations, but the combination of complementary methods does allow the desolvation to be understood. Water and solvent are shown to be lost simultaneously, with no evidence of an intermediate form or increased mobility of the hydrogen-bonded water molecules. The results are consistent with a model in which structural collapse and rearrangement follows the loss of a small fraction of the solvent molecules from the channel structure, with the final form produced being very sensitive to the presence of water vapour during desolvation. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:176–186, 2012

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