Cocrystals of Active Pharmaceutical Ingredients—Praziquantel in Combination with Oxalic, Malonic, Succinic, Maleic, Fumaric, Glutaric, Adipic, And Pimelic Acids

Abstract

The combination of racemic praziquantel, (RS)-PZQ, with aliphatic dicarboxylic acids of the homologous series HOOC–(CH2)n–COOH (with n = 0–8) and the unsaturated analogues of succinic acid as cocrystal formers via liquid-assisted grinding provided a total of nine 1:1 and 2:1 cocrystals with oxalic acid, malonic acid, succinic acid (two polymorphic phases), maleic acid, fumaric acid, glutaric acid, adipic acid, and pimelic acid. The cocrystalline phases were identified first by XRPD analysis and then structurally characterized by IR spectroscopy and, as far as possible, by single-crystal X-ray diffraction analysis. Crystals suitable for XRD analysis were obtained for seven cocrystals and, additionally, for (RS)-PZQ. The analysis of the supramolecular interactions in the crystal structures has shown that the dominant hydrogen bonding patterns within the cocrystals are heterodimeric motifs formed through O–H···O hydrogen bonds between PZQ and the dicarboxylic acids, which mostly contain additionally at least...