Study on the Adsorption Behavior of Preservatives in Multidose Eye Drops and Their Interaction with Packaging Materials

With the increasing prevalence of dry eye syndrome and an aging population, multidose eye drops have become predominant in the market due to their convenience. However, the stability of the antimicrobial efficacy is crucial for patient safety, with the interaction between preservatives and packaging materials being particularly significant. This study systematically examined the effects of packaging material type, pH value, preservative type, and formulation components on the adsorption behavior using single-factor experiments, orthogonal design, X-ray photoelectron spectroscopy (XPS) analysis, and quantum mechanical calculations. The research showed that chlorobutanol exhibited the most significant adsorption (12.5% originates from single-factor analysis), and the degree of adsorption was closely related to the solution environment and the surface chemical properties of the materials. Orthogonal experiments indicated that the type of packaging material and the type of active pharmaceutical ingredient were the primary factors influencing preservative adsorption; the type of pH-adjusting agent had no significant effect on preservative adsorption; however, the solution pH acted synergistically with the preservative to influence its adsorption. XPS analysis revealed a synergistic effect between physical and chemical adsorption, while quantum mechanical calculations further demonstrated that the HOMO energy value (with more negative values indicating stronger adsorption) played a key role in determining the adsorption strength. This study provides a scientific basis for the formulation design and packaging material selection of eye drops, helping to enhance product safety and efficacy.