Comparison of the Protective Effect of Polysorbates, Poloxamer and Brij on Antibody Stability Against Different Interfaces
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. Show more
Publication status
publishedExternal links
Journal / series
Journal of Pharmaceutical SciencesVolume
Pages / Article No.
Publisher
ElsevierSubject
Monoclonal antibody(s); Protein formulation(s); Interfaces; Surfactant; Polysorbates; Poloxamer 188; Brij 35; Protein aggregation; StabilityOrganisational unit
09572 - Arosio, Paolo / Arosio, Paolo
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