Abstract：
Introduction: The hydrogen-bonded networks play a significant role in influencing several physicochemical properties of ofloxacin in artificial tears (ATs), including density, pH, viscosity, and self-diffusion coefficients. The activities of the ofloxacin antibiotic with Ats mixtures are not solely determined by their concentration but are also influenced by the strength of the hydrogen bonding network which highlight the importance of considering factors such as excessive tear production and dry eye conditions when formulating appropriate dosages of ofloxacin antibiotics for eye drops. Objectives: Investigating the physicochemical properties of ofloxacin-ATs mixtures, which serve as a model for understanding the impact of hydrogen bonding on the antimicrobial activity of ofloxacin antibiotic eye drops. Determine the antimicrobial activities of the ofloxacin-Ats mixture with different concentration of ofloxacin. Methods: The ofloxacin-ATs mixtures were analyzed using 1H-NMR, Raman, and UV-Vis spectroscopies, with variation of ofloxacin concentration to study its dissociation kinetics in ATs, mimicking its behavior in human eye tears. The investigation includes comprehensive analysis of 1H-NMR spectral data, self-diffusion coefficients, Raman spectroscopy, UV-Vis spectroscopy, liquid viscosity, and acidity, providing a comprehensive assessment of the physicochemical properties. Results: Analysis of NMR chemical shifts, linewidths, and self-diffusion coefficient curves reveals distinct patterns, with peaks or minima observed around 0.6 ofloxacin mole fraction dissociated in ATs, indicating a strong correlation with the hydrogen bonding network. Additionally, the pH data exhibits a similar trend to viscosity, suggesting an influence of the hydrogen bonding network on protonic ion concentrations. Antibacterial activity of the ofloxacin-ATs mixtures is evaluated through growth rate analysis against Salmonella typhimurium, considering varying concentrations with mole fractions of 0.1, 0.4, 0.6, 0.8, and 0.9. Conclusions: The antibiotic-ATs mixture with a mole fraction of 0.6 ofloxacin exhibited lower activity compared to mixtures with mole fractions of 0.1 and 0.4, despite its lower concentration. The activities of the mixtures are not solely dependent on concentration but are also influenced by the strength of the hydrogen bonding network. These findings emphasize the importance of considering tear over-secretion and dry eye problems when designing appropriate doses of ofloxacin antibiotics for eye drop formulations.
摘要：
介绍：氢键网络在影响人工泪液（AT）中氧氟沙星的几种理化性质中起着重要作用，包括密度，pH值,粘度,和自扩散系数。氧氟沙星抗生素与Ats混合物的活性不仅取决于其浓度，而且还受到氢键网络强度的影响，这突出了在配制适当剂量的氧氟沙星抗生素滴眼液时考虑诸如过量眼泪产生和干眼状况等因素的重要性。目标：研究氧氟沙星-ATs混合物的理化性质，作为理解氢键对氧氟沙星抗生素滴眼液抗菌活性影响的模型。用不同浓度的氧氟沙星测定氧氟沙星-Ats混合物的抗菌活性。方法：使用1H-NMR分析氧氟沙星-ATs混合物，拉曼,和紫外可见光谱，随着氧氟沙星浓度的变化，研究其在ATs中的解离动力学，模仿它的行为在人的眼睛的眼泪。调查包括对1H-NMR光谱数据的全面分析，自扩散系数，拉曼光谱,紫外-可见光谱,液体粘度,酸度,提供对物理化学性质的全面评估。结果：NMR化学位移分析，线宽,自扩散系数曲线揭示了不同的模式，在ATs中解离的氧氟沙星摩尔分数约为0.6的峰或最小值，表明与氢键网络有很强的相关性。此外,pH数据显示出与粘度相似的趋势，表明氢键网络对质子离子浓度的影响。通过对鼠伤寒沙门氏菌的生长速率分析来评估氧氟沙星-ATs混合物的抗菌活性，考虑摩尔分数为0.1、0.4、0.6、0.8和0.9的不同浓度。结论：与摩尔分数为0.1和0.4的混合物相比，氧氟沙星摩尔分数为0.6的抗生素-ATs混合物的活性较低，尽管浓度较低。混合物的活性不仅取决于浓度，而且还受到氢键网络强度的影响。这些发现强调了在设计用于滴眼液制剂的适当剂量的氧氟沙星抗生素时考虑泪液过度分泌和干眼问题的重要性。
