Conformational polymorphic changes in the crystal structure of the chiral antiparasitic drug praziquantel and interactions with calcium carbonate

Praziquantel is an antiparasitic drug used for decades. Currently, the praziquantel commercial preparation is a racemic mixture, inwhich only the levo-enantiomer possesses anthelmintic activity. The knowledge of its properties in the solid state and other chemical-physical properties is necessary for improving its efficacy andapplications. Drug solid dispersions were prepared with calcium carbonate at 1:5 drug to excipient weight ratio by solventevaporation method. Then, the modification of the crystalstructure of the racemic polymorph of praziquantel in presence of calcium carbonate has been studied by means of several analytical techniques (DSC,TGA, XRD, SEM, FTIR, Raman specttroscopy and chiral liquid chromatography). This study has beencompleted with atomistic calculations based on empirical interatomic force fields and quantum mechanics methods applied to the crystal structure of praziquantel andof intermolecular interactions. The results evidenced that calcium carbonate provoked a conformational change in the praziquantel molecule yielding the formation of different polymorphs of praziquantel crystal. These alterations were not observedreplacing calcium carbonate with collodial silica as excipient in the soliddispersion.