Géraldine Springuel

On the influence of using a zwitterionic coformer for cocrystallization: structural focus on naproxen–proline cocrystals

Four original cocrystal structures incorporating a zwitterionic amino acid, prolinium, and a therapeutical agent from profen pharmaceutical family, naproxen, are highlighted and characterized in this study. Powder X-ray diffraction and differential scanning calorimetry permits the observation of the formation of the new structures, obtained by liquid-assisted grinding with methanol. Single-crystal X-ray diffraction gives us a precise outlook of the crystalline network, and allows us to accurately determine the main structural supramolecular synthon: column-like motifs, formed by prolinium entities, around whom the pharmaceutical coformer is organized. From comparison with the CSD, a similar structural pattern emerged in several other structures incorporating prolinium moieties, but not in the case of cocrystals incorporating naproxen and other non-zwitterionic coformers. This result leads us to the conclusion that zwitterionic compounds, such as amino acids, can force a pharmaceutical coformer to structure itself following a known common motif guided only by the zwitterionic entity; a very challenging aspect to take into account when developing new solid forms of therapeutical agents.

Ternary and quaternary phase diagrams: Key tools for chiral resolution through solution cocrystallization

The goal of this contribution is to guide the reader through the construction and the understanding of quaternary phase diagrams in the pursuit of optimal conditions for a chiral resolution through cocrystallization in solution. The overall description will be illustrated by experimental results on a system involving RS-2-(2-oxopyrrolidin-1-yl) butanamide as chiral API to be separated, and S-mandelic acid as chiral coformer.