Mechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties

Praziquantel (PZQ) is the first-line drug used against schistosomiasis, one of the most common parasitic diseases in the world. A series of crystalline structures including two new polymorphs of the pure drug and a series of cocrystals of PZQ have been scovered and deposited in the Cambridge Structural Database (CSD). This work adds to the list of ulticomponent forms ofPZQa relevant example of a racemic mihydrate (PZQ-HH), obtainable fromcommercialPZQ(polymorphic Form A) through chanochemistry. Noteworthy, the formation of the new hemihydrate strongly depends on the initial polymorphic form of PZQ and on the experimental conditions used. The new PZQ-HH has been fully characterized by means of HPLC, Dierential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Hot-Stage Microscopy (SEM), Powder X-Ray Diraction (PXRD), Scanning Electron Microscopy (SEM), FT-IR, olarimetry, solid-state NMR (SS-NMR), solubility and intrinsic dissolution rate (IDR), and in vitro tests on Schistosoma mansoni adults. The crystal structure was solved from the powder X-ray diraction pattern and validated by periodic-DFT calculations. The new bioactive hemihydrate was physically stable for three months and showed eculiar biopharmaceutical features including enhanced solubility and a double ntrinsic ssolution rate in water in comparison to the commercially available PZQ Form A.