Advantages of cocrystallization in the field of solid-state pharmaceutical chemistry: l-Proline and MnCl 2

Abstract

Cocrystallization (formation of a “ cocrystal”) is an emerging method to optimize physico-chemical properties of pharmaceutically active compounds. One elegant technique used to obtain such cocrystals is grinding the components together, either alone or in the presence of a small amount of solvent (so called solvent-drop grinding). Dry grinding has been used here to obtain cocrystals (actually a hydrated salt) of l-Proline and MnCl 2. In that context, a new crystalline structure of a multicomponent molecular complex composed of l-Proline and MnCl 2 is here reported. The complex was characterized by powder and single-crystal X-ray diffraction and differential scanning calorimetry. This study underlines the interest of grinding as a method to synthesize original solid-state complexes. It also emphasizes the advantage of combining calorimetric and X-ray diffraction to characterize the newly formed solids. Finally, our work provides structural basis for the role that l-Proline can play within multicomponent solid-state molecular complexes, in particular as a potential cocrystal former acting by both ionic and H-bond interactions when combined to molecules of pharmaceutical interest.