Comparing and Quantifying the Efficiency of Cocrystal Screening Methods for Praziquantel

• Published in: Crystal growth & design Vol. 22; no. 9; pp. 5511 - 5525
• Main Authors: Charpentier, Maxime D., Devogelaer, Jan-Joris, Tijink, Arnoud, Meekes, Hugo, Tinnemans, Paul, Vlieg, Elias, de Gelder, René, Johnston, Karen, ter Horst, Joop H.
• Format: Journal Article
• Language: English
• Published: American Chemical Society 07.09.2022
• Subjects: Chemical and Process Engineering; Chemical engineering; Chemical Sciences; Condensed Matter; Engineering Sciences; Material chemistry; Materials; Materials Science; Physics
• ISSN: 1528-7483; 1528-7505
• DOI: 10.1021/acs.cgd.2c00615

Pharmaceutical cocrystals are highly interesting due to their effect on physicochemical properties and their role in separation technologies, particularly for chiral molecules. Detection of new cocrystals is a challenge, and robust screening methods are required. As numerous techniques exist that differ in their crystallization mechanisms, their efficiencies depend on the coformers investigated. The most important parameters characterizing the methods are the (a) screenable coformer fraction, (b) coformer success rate, (c) ability to give several cocrystals per successful coformer, (d) identification of new stable phases, and (e) experimental convenience. Based on these parameters, we compare and quantify the performance of three methods: liquid-assisted grinding, solvent evaporation, and saturation temperature measurements of mixtures. These methods were used to screen 30 molecules, predicted by a network-based link prediction algorithm (described in Cryst. Growth Des. 2021, 21(6), 3428–3437) as potential coformers for the target molecule praziquantel. The solvent evaporation method presented more drawbacks than advantages, liquid-assisted grinding emerged as the most successful and the quickest, while saturation temperature measurements provided equally good results in a slower route yielding additional solubility information relevant for future screenings, single-crystal growth, and cocrystal production processes. Seventeen cocrystals were found, with 14 showing stability and 12 structures resolved.