Phase Diagrams of Praziquantel and Vanillic Acid Cocrystals: Racemic Compound and Conglomerate System
Charline J. J. Gerard, Clément Pinètre, Hugo Cercel, Maxime D. Charpentier, Morgane Sanselme, Nicolas Couvrat, Clément Brandel, Yohann Cartigny, Valérie Dupray, Joop H. ter Horst
Abstract
Praziquantel (PZQ) is widely used to treat schistosomiasis. However, this chiral active pharmaceutical ingredient (API) is still produced as a racemic compound while only the ( R )-enantiomer is active. A possible way to control the solid properties of chiral APIs and herewith to separate the enantiomers is their cocrystallization with a coformer to form a conglomerate cocrystal. Vanillic acid (VA) has been previously identified as a coformer able to form two different cocrystal forms with PZQ. While the first one has been characterized and identified as an equimolar racemic cocrystal (i.e., a 1:1 (±)PZQ:VA racemic cocrystal), the properties of the second cocrystal remain unknown. In this paper, a variety of analytical methods (XRPD, DSC, and SHG) have been used to characterize the second cocrystal form. The results show that this second cocrystal form is a 1:2 (+)/(−)PZQ:2VA cocrystal, which crystallizes as a conglomerate, opening routes toward the separation of PZQ enantiomers through preferential crystallization. This study shows the importance of testing several stoichiometries in a screening context, as the desired form or properties, such as a conglomerate cocrystal, could be found in a nonequimolar cocrystal.