A Maze of Solid Solutions of Pimobendan Enantiomers: An Extraordinary Case of Polymorph and Solvate Diversity
2017-12-04T00:00:00Z (GMT) by
Over 10 polymorphs and solvatomorphs of the chiral pharmaceutically active ingredient pimobendan were found to lack enantioselectivity in the solid state, accordingly, forming solid solutions of enantiomers, which is reported to be a rare phenomenon. Solid form screening was performed on different enantiomeric composition samples to analyze obtained phases with powder X-ray diffraction and thermogravimetric differential scanning calorimetry. For nonsolvated forms, a melt phase diagram has been constructed convincingly showing the existence of stable and metastable solid solutions near the pure enantiomer and around the racemic composition regions. A crystal structure study combined with solid-state NMR experiments was performed to analyze and explain structural aspects of pimobendan solid solutions. Furthermore, the driving force for the existence of such a surprisingly large amount of different solid state phases lacking enantioselectivity for a single compound is elucidated tracking down the origin of their formation to the molecular level.
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