Centre for Research on Drug Repurposing, Institute of Life Sciences, University of Hyderabad, Hyderabad 500 046, India.
School of Chemistry, University of Hyderabad, Prof. C.R. Rao Road, Gachibowli, Central University PO, Hyderabad 500 046, India.
J Pharm Sci. 2011 Aug;100(8):3160-3176. doi: 10.1002/jps.22537. Epub 2011 Mar 10.
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.
氟喹诺酮类抗生素诺氟沙星和环丙沙星与羧酸形成了六种新盐，这些盐通过红外光谱、差示扫描量热法、X 射线粉末衍射和单晶 X 射线衍射进行了表征。其中五种盐是具有不同含水量的水合物。从晶体结构中证实了这些盐中的分子组成、化学计量和质子转移状态。报告了羧酸阴离子（如草酸盐、酒石酸盐、苯甲酸盐、丙二酸盐和柠檬酸盐）和水合状态对药物盐在纯水中（pH 6.4）、0.1 N HCl（pH 1.2）和磷酸盐缓冲溶液（pH 6.8）中的溶解度和溶解曲线的影响。这些盐在纯水中和磷酸盐缓冲介质中的溶解度和溶解速度比参比药物更快，但在酸性介质中的顺序相反。这些盐在溶解测量条件下化学稳定，而参比药物诺氟沙星在实验结束时会向诺氟沙星水合物发生相转变。
