MS31-P16 Access to Several Crystalline Forms of R-Encenicline Hydrochloride Using Desolvation of Various SolvatesR-Encenicline (N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-chloro-1-benzothiophene-2-carboxamide) hydrochloride (Enc-HCl) is a partial, selective agonist of the α-7 nicotinic acetylcholine receptor. It is being developed for the treatment of cognitive deficits in schizophrenia and Alzheimer's disease. Previously, three monohydrates (I, II and X) were reported in the patent , recently we reported fourth polymorph of Enc-HCl monohydrate (III) as well as four dehydrates of all monohydrates (ID, IID and IIID) .
The solid state landscape of Enc-HCl presents several more nonsolvated polymorphic forms as well as large number of solvates. Almost all of these polymorphic forms (V, VI,VII,VIII,IX) can only be obtained by means of desolvation of different solvates. Moreover, depending on the different desolvation conditions two different polymorphs can be obtained from the same acetic acid disolvate (SAA). Indeed, when the desolvation process is performed in elevated temperature - polymorph VIII is produced, but in dry gas flow - polymorph IX. The only polymorph that is accessible without the parent solvated phase is form IV.
The crystal structures of six polymorphs as well as their precursors have been determined directly from powder diffraction data. The crystal structures of precursors were found to be relatively structurally similar and related to those of desolvated phases, which was consistent with the observed phase transitions among the related pairs. In addition, a comparison of the thermodynamic stability of polymorphs were performed using DFT calculations, differential scanning calorimetry data and solvent mediated slurry-bridging experiments. References:
 Oliver-Shaffer, P. et al. (2014). U.S. Patent 2014/0249179,
 Kons, A. et al. (2018) Cryst. Growth Des., 18, 2100–2111.Keywords: encenicline, polymorphs, solvates