The New Gatifloxacin‐p‐Coumaric Acid Cocrystalline Form for Enhanced In Vitro Pharmaceutical Properties While Improving Oral Bioavailability and Antibacterial Activity

Abstract

AbstractA molecular salification strategy of double majorization and synergistic improvement efficacy has been submitted, aiming at getting utmost out of the advantages of phenolic acid nutrient p‐coumaric acid (CMA) to improve the pharmaceutical properties of antibacterial agent gatifloxacin (GAT). The present strategy applies the saltforming capacity of CMA interacting with GAT to self‐assemble a new molecular salt, thereby improving the in vitro physicochemical performances of GAT and further perfecting its in vivo pharmacokinetics, as well as enhancing the antibacterial effectiveness of GAT. Guided by this strategy, the novel GAT‐phenolic acid nutrient molecular salt, named GAT‐CMA, is directionally prepared with its precise structure analyzed by single crystal X‐ray diffraction. The results show that proton transfer occurs between the piperazine N of GAT and the carboxyl group of CMA, thus altering the intermolecular interaction mode of GAT itself, breaking the relatively stable zwitterionic state, displaying a circular stacking structure dominated by [GAT+‐CMA−], which is conducive to the improvement of GAT's physicochemical properties. Interestingly, the enhanced properties in vitro effectively translate into pharmacokinetic merits in vivo, showing improved bioavailability. More importantly, due to the synergistic antibacterial effect of GAT and CMA, the antibacterial ability of molecular salt has also been effectively enhanced.