Polymorphs of praziquantel–succinic acid cocrystal: crystal structure, thermodynamic relationship, and improved pharmaceutical performance

Polymorphism is a ubiquitous phenomenon of critical significance for the pharmaceutical industry, yet reports on cocrystal polymorphs are scarce. This study elucidates the crystal structure of the praziquantel (PZQ)-succinic acid (SUC) cocrystal polymorph, α-PZQ-SUC. The dominant supramolecular interaction in the cocrystal polymorph is the O−H···O hydrogen bond between SUC and PZQ, consistent with the supramolecular interaction in the previously reported β-PZQ-SUC polymorph. Comprehensive analysis, including thermal analysis, theoretical calculations, and solvent-mediated polymorphic transformation experiments, established a monotropic relationship between the two polymorphs, with α-PZQ-SUC demonstrating greater stability than β-PZQ-SUC. Both α-PZQ-SUC and β-PZQ-SUC enhance the solubility and dissolution behavior of PZQ, indicating their suitability for pharmaceutical applications based on improved pharmaceutical performance.