Comparison of the Protective Effect of Polysorbates, Poloxamer and Brij on Antibody Stability Against Different Interfaces

Dominik Zürcher; Severin Caduff; Laetitia Aurand; Umberto Capasso Palmiero; Klaus Wuchner; Paolo Arosio

doi:10.1016/j.xphs.2023.06.004

Comparison of the Protective Effect of Polysorbates, Poloxamer and Brij on Antibody Stability Against Different Interfaces

J Pharm Sci. 2023 Nov;112(11):2853-2862. doi: 10.1016/j.xphs.2023.06.004. Epub 2023 Jun 7.

Authors

Dominik Zürcher¹, Severin Caduff¹, Laetitia Aurand¹, Umberto Capasso Palmiero¹, Klaus Wuchner², Paolo Arosio³

Affiliations

¹ Department of Chemistry and Applied Biosciences, ETH Zürich, Zürich, Switzerland.
² Janssen R&D, BTDS Analytical Development, Schaffhausen, Switzerland.
³ Department of Chemistry and Applied Biosciences, ETH Zürich, Zürich, Switzerland. Electronic address: paolo.arosio@chem.ethz.ch.

PMID: 37295604
DOI: 10.1016/j.xphs.2023.06.004

Abstract

Therapeutic proteins and antibodies are exposed to a variety of interfaces during their lifecycle, which can compromise their stability. Formulations, including surfactants, must be carefully optimized to improve interfacial stability against all types of surfaces. Here we apply a nanoparticle-based approach to evaluate the instability of four antibody drugs against different solid-liquid interfaces characterized by different degrees of hydrophobicity. We considered a model hydrophobic material as well as cycloolefin-copolymer (COC) and cellulose, which represent some of the common solid-liquid interfaces encountered during drug production, storage, and delivery. We assess the protective effect of polysorbate 20, polysorbate 80, Poloxamer 188 and Brij 35 in our assay and in a traditional agitation study. While all nonionic surfactants stabilize antibodies against the air-water interface, none of them can protect against hydrophilic charged cellulose. Polysorbates and Brij increase antibody stability in the presence of COC and the model hydrophobic interface, although to a lesser extent compared to the air-water interface, while Poloxamer 188 has a negligible stabilizing effect against these interfaces. These results highlight the challenge of fully protecting antibodies against all types of solid-liquid interfaces with traditional surfactants. In this context, our high-throughput nanoparticle-based approach can complement traditional shaking assays and assist in formulation design to ensure protein stability not only at air-water interfaces, but also at relevant solid-liquid interfaces encountered during the product lifecycle.

Keywords: Brij 35; Interfaces; Monoclonal antibody(s); Poloxamer 188; Polysorbates; Protein aggregation; Protein formulation(s); Stability; Surfactant.