2024 AIChE Annual Meeting

(172d) Light-Induced Oxidation of Polysorbate 80 in Citrate Buffer with Glutathione Disulfide (GSSG) and Trace Iron

Authors

Ke, G., The University of Kansas
Schoneich, C., The University of Kansas
Dhar, P., University of Kansas
Polysorbate 80 (PS80) stands out as a versatile surfactant extensively used in the development of stable pharmaceutical formulations. Among its most important applications is the formulation of protein therapeutics, where polysorbate is added to prevent interfacial stress, primarily by protecting the air-liquid interface against protein adsorption. However, PS80 is susceptible to degradation via oxidation and hydrolysis, which presents a significant challenge for formulators focused on maintaining the stability of protein-based biotherapeutic products. Oxidative degradation of PS80 can be induced during manufacturing and storage as a result of light exposure and due to the presence of metals in trace amounts. Specifically, it has been shown that in the presence of peptides and trace amounts of iron, PS80 formulated in citrate buffer can undergo the cis/trans isomerization of PS80 fatty acids (Prajapati et al., 2022). However, how this change alters the surface activity of PS80 is unknown. In this work, we studied the surface activity of PS80 formulations in citrate buffer when exposed to UVA radiation. To emulate a protein formulation environment, we added trace amounts of iron, and glutathione disulfide (GSSG) as a disulfide donor. The surface pressure of surfactant formulations was monitored during surfactant adsorption to the air-solution interface, and the surfactant’s critical micelle concentration (CMC) was evaluated by tensiometry and fluorescence micelle assay. Our results together showed significant changes in the surface activity of PS80 solutions following light exposure. Specifically, a tenfold shift in the CMC value was observed. Analytical studies of the PS80 composition of samples aspirated from the interface showed the presence of both cis and trans forms of PS80, which may explain the shift in the CMC. These findings demonstrate the importance of understanding the surface-active properties of PS80 under various conditions for the development of stable drug formulations.

References:

Prajapati I., Subelzu N., Zhang Y., Wu Y., Schoneich C. (2022). J. Pharm. Sci., 111, 991-1003