Improving solubility and intrinsic dissolution rate of ofloxacin API through salt formation via mechanochemical synthesis with diphenic acid

Abstract

The study focusses on the effect of solubility and intrinsic dissolution rate on the pharmaceutical salt of ofloxacin, a new generation fluoroquinolone antibacterial marketed drug, with the organic acid coformer, diphenic acid produced via mechanochemical synthesis using liquid assisted grinding method. The synthesized cocrystal salt was characterized by single crystal and powder X-ray diffraction, differential scanning calorimetry, and infrared spectroscopy techniques. The crystal structure reveals that, there is proton migration from the coformer to the drug leading to the formation of salt via charge assisted N–H+···O hydrogen bond interactions. The aqueous solubility of the drug and its corresponding salt were determined in neutral phosphate buffer medium (pH = 7) at 25 °C using UV–Vis absorption spectroscopy, while dissolution experiments were carried out at 37 °C bath temperature and neutral phosphate buffer conditions. Interestingly it has been observed that the aqueous solubility and intrinsic dissolution rate of the salt form of ofloxacin has enhanced significantly compared to the parent drug and this is expected to have implications in the bioavailability of the drug in different formulations related to the utilization of this drug.