Study on the Structure, Solubilities, Antibacterial Activities and In Vivo Toxicity of Hesperetin and Norfloxacin Cocrystal

Drug-drug cocrystals can improve the physical and pharmaceutical properties of drugs and have been widely studied by many researchers. A new pharmaceutical cocrystal [C₁₆H₁₈FN₃O₃][C₁₆H₁₄O₆] · 2(C₂H₅OH) (HSP-NOR) was synthesized by hesperetin (HSP) and norfloxacin (NOR) with the aim of improving the antibacterial activity and physicochemical properties. The single crystal structure shows that the asymmetric unit comprises both hesperetin and norfloxacin, as well as two ethanol molecules, in which norfloxacin exists as a zwitterion. The cocrystal formation improves the solubilities of hesperetin and norfloxacin in pure water. Preliminary antibacterial experiments showed that the antibacterial activities of the cocrystal on Streptococcus pneumoniae, Escherichia coli, Shigella dysenteriae, and Pseudomonas aeruginosa were stronger than those of norfloxacin. The in vivo study of acute toxicity showed that the minimum lethal dose of the cocrystal to mice was >3000 mg kg^-1 BW, and there were no signs of toxicity after oral administration at this dosage.