Novel Hydrate and Anhydrate Cocrystals/Salts of Norfloxacin and Their Physicochemical Properties

Abstract

The low solubility and low permeability of Biopharmaceutics Classification System BCS class IV antibiotic drug norfloxacin (NORF) were studied for improvement of physicochemical properties in hydrated and anhydrous cocrystals/salts of NORF with methyl paraben (MBZ), ethyl paraben, methanesulfonic acid (MSA), benzenesulfonic acid (BSA), p-toluenesulfonic acid (PTSA), and tyramine (TYM). These crystalline forms were characterized by powder X-ray diffraction (PXRD), thermal [differential scanning calorimetry (DSC)], gravimetric [thermogravimetric analysis (TGA)], spectroscopic [infrared (IR)], and microscopy [scanning electron microscopy (SEM)] techniques. The crystal structures of NORF-MBZ-HYD, NORF-MSA-HYD, NORF-PTSA, and NORF-TYM-HYD were analyzed by single-crystal X-ray diffraction. Further, the hydrated and anhydrous forms were characterized by IR, DSC, and TGA to understand the hydration and dehydration events and by field emission SEM for crystal morphology and shape/size characteristics. Solubility, dissolution, and diffusion measurements showed that NORF anhydrous forms are more soluble and diffusible than their corresponding hydrated forms. Notably, NORF ionic crystal forms with MSA and BSA are highly soluble with good dissolution rates and high cumulative drug diffusion.