Fluoroquinolone Salts with Carboxylic Acids

The crystallization of fluoroquinolone antibiotics norfloxacin and ciprofloxacin with carboxylic acids gave six new salts that were characterized by infrared spectroscopy, differential scanning calorimetry, X-ray powder diffraction, and single crystal X-ray diffraction. Five of these salts are hydrates with different levels of water content. The molecular composition, stoichiometry, and proton transfer state in these salts are confirmed from the crystal structure. The effect of carboxylate counterion, such as oxalate, tartarate, benzoate, malonate, and citrate, and hydration state on the solubility and dissolution profile of drug salts are reported in pure water (pH 6.4), 0.1 N HCl (pH 1.2), and phosphate buffer solution (pH 6.8). These salts are more soluble and exhibit faster dissolution in pure water and phosphate buffer medium than the reference drugs, but the order is reversed in acidic medium. These salts are chemically stable to the dissolution measurement conditions, whereas the reference drug norfloxacin undergoes phase transformation to norfloxacin hydrate at the end of the experiment. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:3160-3176, 2011