Drug Formulation Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., 301 Gensuke, Fujieda, Shizuoka 426-8646, Japan.
Int J Pharm. 2011 May 30;410(1-2):23-30. doi: 10.1016/j.ijpharm.2011.03.006. Epub 2011 Mar 22.
The content of latanoprost is likely to decrease in solution because of the adsorption to eye drop containers and hydrolysis. We reduced these problems and established a formulation of latanoprost eye drops which is stable at room temperature. We assume that the additive surfactants form micelles and stabilize latanoprost in this formulation. In this study, we elucidated the latanoprost stabilization mechanism. It was revealed by Arrhenius analysis that the adsorption to eye drop containers and hydrolysis of latanoprost were temperature-dependent. In addition, polyethylene glycol monostearates inhibited the adsorption and hydrolysis of latanoprost at 1 mg/mL, which exceeded the critical micelle concentration. By the fluorescent probe method, it was suggested that the surfactants were associated with benzalkonium chloride and formed complex micelles consisting of about 10 molecules, and latanoprost interacted with the micelles at 1:1. By (1)H NMR, it was revealed that adsorption was inhibited by arranging the hydrophobic group toward the center of complex micelles and that hydrolysis was inhibited by interaction between the ester group and the complex micelles. It was shown that the latanoprost is stabilized by the interaction with complex micelles. It was effective for the inhibition of both adsorption and degradation.
由于滴眼容器的吸附和水解，拉坦前列素的含量可能会降低。我们减少了这些问题，并建立了一种在室温下稳定的拉坦前列素滴眼液配方。我们假设添加剂表面活性剂形成胶束并在这种配方中稳定拉坦前列素。在这项研究中，我们阐明了拉坦前列素的稳定机制。通过阿仑尼乌斯分析表明，滴眼容器的吸附和拉坦前列素的水解都与温度有关。此外，当聚乙二醇单硬脂酸酯的浓度为 1mg/mL 时，超过临界胶束浓度，它可以抑制拉坦前列素的吸附和水解。通过荧光探针法，表明表面活性剂与苯扎氯铵结合形成由约 10 个分子组成的复合胶束，拉坦前列素与胶束以 1:1 的比例相互作用。通过 1H NMR 表明，通过将疏水性基团排列在复合胶束的中心，可以抑制吸附，通过酯基与复合胶束的相互作用可以抑制水解。表明拉坦前列素通过与复合胶束的相互作用而稳定。这对于抑制吸附和降解都很有效。
