Enhancing the Screening Efficiency of Chiral Cocrystals for the Separation of Praziquantel through the Use of Coformer Derivatives

Cocrystallization has become an increasingly attractive method for the separation of chiral active pharmaceutical ingredients (API). However, the screening process of coformers (CFs) that are capable of cocrystallizing with the API and further producing chiral cocrystals suitable for enantiomeric resolution is often time-consuming and may not always give the desired results. One of the promising approaches involves the prediction of suitable CF structures based on the modification of the structure of a known successful CF for a particular target molecule. This can lead to the formation of new cocrystals with different chiral space groups that may be more suitable for chiral resolution. In this study, we propose four CF structures similar to malic acid, which has been shown to form diastereomeric cocrystals with praziquantel (PZQ), including tartaric acid, methylsuccinic acid, 2,3-dimethylsuccinic acid, and 2,2-dimethylsuccinic acid. Our findings demonstrated that these four CFs can generate new cocrystal structures with PZQ and some structures crystallized in a Sohncke space group, which allows only for an enantiomerically pure crystal structure. Notably, meso-2,3-dimethylsuccinic acid shows the potential for forming a rare conglomerate cocrystal. Furthermore, the energetic formation of some cocrystals was revealed by a DFT calculation.