Polymorphism of Praziquantel: Role of Cooling Crystallization in Access to Solid Forms and Discovery of New Polymorphs

Abstract

Praziquantel (PZQ) is an anthelmintic first-line drug to treat schistosomiasis, a neglected tropical disease strongly related to poverty. PZQ crystalline structures and polymorphs have been studied mainly via mechanochemical approaches. This work applies a systematic study to investigate the polymorphism of PZQ using cooling crystallization experiments under different conditions not yet explored in the literature for this compound. We accessed all forms previously reported so far obtained via mechanochemistry and the hydrate found through supercritical CO2 processing. A novel dimethylacetamide (DMA) solvate was obtained, and a new form was discovered after desolvation of the DMA solvate by aging and exposure to water-vapor atmosphere. Toluene and triethylamine were solvents capable of enabling the formation of different forms depending on the employed experimental condition. A new form was discovered using triethylamine as solvent, which differs from all known polymorphs. The results of this work demonstrate that solvent selection and variation in the rate of supersaturation generation can generate forms obtained from more complicated techniques as well as potentially finding new forms.