a. Department of Physical Chemistry, University of Latvia, Jelgavas 1, Riga 1004, Latvia

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.

a. Department of Physical Chemistry, University of Latvia, Jelgavas 1, Riga 1004, Latvia

Encenicline hydrochloride (Enc-HCl) crystallizes in four different monohydrate phases, but at the same time crystallization in a nonsolvated phase is not observed, indicating that water plays a crucial role in guiding the crystallization process and ensuring structure stability. All monohydrate phases show exceptionally high stability, and the main structural motif stays intact even after dehydration, leading to isostructural (for I and II) or isomorphic (for III) desolvates. Three monohydrate phases with determined crystal structure information consists of Enc-HCl-water hexamers that are stacked into similar slabs, that are further packed identically in monohydrates I, II, and III. The features of these hexamer slabs determine the properties of the Enc-HCl monohydrates and dehydrates, the dehydration mechanism, and stability of each phase. It was justified that in the Enc-HCl system efficient intermolecular interactions provided by the incorporation of water in the crystal structure play a crucial role in stabilization of the structures.

a. Department of Physical Chemistry, University of Latvia, Jelgavas 1, Riga 1004, Latvia

In structural study of seven bile acids it was identified that their propensity for solvate formation is directly related to the packing efficiency of the unsolvated phases: low packing index, voids, and unsatisfied hydrogen bonding lead to extensive solvate formation, whereas efficient packing leads to the opposite. This was determined to be caused by the presence of OH group attached to carbon C12. Solvate formation was determined to provide a noticeable improvement in the packing efficiency for compounds having ansolvates with inefficient packing.

a. Department of Physical Chemistry, University of Latvia, Jelgavas 1, Riga 1004, Latvia

b. Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstraße 1, 39106 Magdeburg, Germany

c. Ecole polytechnique fédérale de Lausanne, Route Cantonale, 1015 Lausanne, Switzerland

Over ten polymorphs and solvatomorphs of 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 analyse obtained phases with PXRD and TG/DSC. For non-solvated forms a melt phase diagram has been constructed convincingly showing 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 analyse and explain structural aspects of pimobendan solid solutions. Furthermore, driving force for 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.