Modifying Antisolvent Addition Technique for Ionic Co-Crystallization of Paracetamol (PCM) and Metal Sulfates

This investigation reports the successful synthesis and characterization of a co-crystal composed of paracetamol (PCM) and metal sulfates of zinc and iron using an adapted antisolvent addition technique which leveraged the antagonistic solvent affinities of PCM and the metal sulfates. Ethanol and water acted as solvents for PCM and the metal sulfates, respectively, while simultaneously serving as antisolvents for the other constituent. Scanning Electron Microscopy (SEM) micrographs revealed crystals exhibiting a rod-like structure and a surface covered by flakes, which are both characteristic features of PCM and zinc sulfate, suggesting the formation of a new crystalline phase. This is further supported by the distinct powder x-ray diffraction pattern for the co-crystal when compared with that of the individual constituents. Analysis of Fourier Transform Infrared (FTIR) spectra suggests that the interacting functional groups which formed a new hydrogen bond network are the amide N-H and the water in the aquo complex formed by the metals in aqueous solutions. The findings highlight the simplicity of the crystallization technique and provide insights into the structural and mechanistic aspects of organic-inorganic co-crystals. This study contributes to the advancement of co-crystal engineering and lays the groundwork for exploring the pharmaceutical and functional applications of PCM-metal sulfate co-crystals.