Piracetam Co-Crystals with OH-Group Functionalized Carboxylic Acids

We report the synthesis, crystal structures, and basic physicochemical properties of six co-crystals of piracetam. Co-crystals of piracetam with L-tartaric acid, with citric acid in a 1:1 and 3:2 ratio, with racemic mandelic acid, and with L-mandelic acid, as well as a piracetam-citric acid ethanol solvate were found in a focused screening approach. Sample amounts of up to several hundred milligrams of each co-crystal were obtained from either solvent-drop grinding, solution evaporation, or crystallization from solution. Crystal structure analysis revealed that the often observed amide-carboxylic acid R-2(2)(8) synthon is rarely found in the herein reported crystal structures. The mentioned motif can be used as a target for hydrogen bonds; however, in presence of a multitude of hydrogen bond donors and acceptors it cannot serve for an anticipation of co-crystals. Compared to piracetam the piracetam-L-tartaric acid co-crystal shows improved hygroscopic properties.