Liang Di, Li Fei, Duan Jingzhong, Sun Wei, Yu Xiaoyan
School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China.
Antibiotics (Basel). 2024 Sep 14;13(9):888. doi: 10.3390/antibiotics13090888.
Norfloxacin (NORF) is a broad-spectrum quinolone that is widely utilized for the treatment of various bacterial infections and is considered one of the most commonly used fluoroquinolone antibiotics. However, NORF's clinical utility is limited by its poor water solubility and relatively low oral bioavailability. This study presents an optimization and synergistic enhancement approach through salt/co-crystal, aiming to maximize the biopharmaceutical properties of NORF with the use of phenolic acid. Following this strategy, two new hydrate salts of NORF with phenolic acid, namely, NORF-3,5-DBA hydrate (salt ) and NORF-VA hydrate (salt ), were prepared and systematically confirmed. Two hydrate salts were produced by means of the slow evaporation crystallization method, and the structures were determined through single-crystal X-ray diffraction (SCXRD). Additionally, powder X-ray diffraction (PXRD), Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and high-performance liquid chromatography (HPLC) were applied to analyze the features of the two salts. The experimental results indicated that the formation of the two salts could enhance the solubility and improve the release behavior of NORF. Interestingly, the physicochemical properties of NORF were significantly improved as a result, leading to an enhancement in its antibacterial activity. This was demonstrated by the enhanced inhibition of bacterial strains and the lower minimum inhibitory concentration values.
诺氟沙星（NORF）是一种广谱喹诺酮类药物，广泛用于治疗各种细菌感染，被认为是最常用的氟喹诺酮类抗生素之一。然而，诺氟沙星的临床应用受到其水溶性差和口服生物利用度相对较低的限制。本研究提出了一种通过盐/共晶的优化和协同增强方法，旨在利用酚酸最大化诺氟沙星的生物药剂学性质。按照该策略，制备并系统确认了诺氟沙星与酚酸的两种新型水合盐，即诺氟沙星-3,5-二苯甲酸水合物（盐 ）和诺氟沙星-香草酸水合物（盐 ）。通过缓慢蒸发结晶法制备了两种水合盐，并通过单晶X射线衍射（SCXRD）确定了其结构。此外，还应用粉末X射线衍射（PXRD）、傅里叶变换红外（FT-IR）光谱、差示扫描量热法（DSC）、热重分析（TGA）和高效液相色谱（HPLC）来分析这两种盐的特性。实验结果表明，两种盐的形成可以提高诺氟沙星的溶解度并改善其释放行为。有趣的是，诺氟沙星的物理化学性质因此得到显著改善，导致其抗菌活性增强。这通过对细菌菌株的抑制增强和最低抑菌浓度值降低得到证明。
