6533b854fe1ef96bd12ae8a0

RESEARCH PRODUCT

On the structural aspects of solid solutions of enantiomers: an intriguing case study of enantiomer recognition in the solid state

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Structural aspects of solid solutions of enantiomers have been considered and the corresponding definitions of type 1 and type 2 solid solutions have been revised based on the available structures reported in the literature. Examples of both types are presented indicating that (e.g., type 1 solid solutions) there is a straightforward relationship between the particular structural aspects and the enantiomer miscibility limits in the solid state. Furthermore, enantiomer recognition in a type 2 solid solution formed by the enantiomers of a pharmaceutically active ingredient, pimobendan, has been studied in more detail. It was found that upon rapid crystallization from a solution a structure possessing a fully disordered enantiomer layout forms. By suspending such a crystalline phase in a solvent over time it tends to form an ordered (racemic compound) state. The study demonstrates that a non-equilibrium crystalline phase reaches the equilibrium state structure, very similar to that determined by an SCXRD study of a slowly grown single crystal. The study also proves that the degree of enantiomer recognition in type 2 solid solutions has a profound thermodynamic origin, unlike that indirectly claimed in some literature sources to be arising from kinetic aspects during the crystal growth.