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A Maze of Solid Solutions of Pimobendan Enantiomers: An Extraordinary Case of Polymorph and Solvate Diversity
journal contribution
posted on 2017-12-04, 00:00 authored by Toms Rekis, Agris Be̅rziņš, Inese Sarceviča, Artis Kons, Ma̅rtiņš Balodis, Lia̅na Orola, Heike Lorenz, Andris ActiņšOver
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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Extraordinary Caseenantiomeric composition samplesracemic composition regionsSolvate Diversitystate phasespowder X-ray diffractioncrystal structure studyscanning calorimetryNMR experimentsSolid form screeningnonsolvated formsPimobendan Enantiomersingredient pimobendanchiral pharmaceuticallySolid Solutions10 polymorphssolutionlack enantioselectivityphase diagram
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