Competitive Surface Activity of Monoclonal Antibodies and Nonionic Surfactants at the Air-Water Interface Determined by Interfacial Rheology and Neutron Reflectometry.

Abstract

Interfacial stresses can destabilize therapeutic formulations containing monoclonal antibodies (mAbs), which is proposed to be a result of adsorption and aggregation at the air-water interface. To increase protein stability, pharmaceutical industries add surfactants, such as Polysorbate 20 (PS20), into protein formulations to minimize mAb adsorption at the interface but rarely quantify this process. We determine that mAb adsorption in surfactant-free solutions creates a monolayer with significant viscoelasticity, which can influence measurements of bulk mAb solution viscosity. In contrast, PS20 absorption leads to an interface with negligible interfacial viscosity that protects the air-water interface from mAb adsorption. These studies were performed through a combined study of surface tensiometry, interfacial rheology, capillary viscometry, and neutron reflectometry to determine the surface activity of a model surfactant, PS20, and mAb system, which can be useful for the successful formulation developments of biotherapeutics.