The stabilization mechanism of latanoprost.

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.