Adsorption and aggregation of monoclonal antibodies at silicone oil-water interfaces

A big challenge in biopharmaceutical development is drug product aggregation, which adversely affects drug quality and safety. Monoclonal antibody (mAb) therapies are rapidly growing for the treatment of various diseases like cancer and autoimmune disorders. Many mAb drug products are sold as pre-filled syringes and vials with liquid formulations. Typically, the walls of pre-filled syringes and stoppers in vials are coated with silicone oil to lubricate the surfaces during use. MAbs are surface-active and adsorb to these silicone oil-solution interfaces, which is an important source of aggregation.

To gain a deeper understanding of the adsorption at these interfaces and to help mitigate the challenge of aggregation, we studied therapeutic formulations containing two different antibodies with different propensities to aggregate at these interfaces. The surface activity was studied through measurements of oil-water interfacial tension, surface mass adsorption (using Quartz Crystal Microbalance, QCM-D) and interfacial rheology. We also investigated the efficacy of surfactants such as polysorbates and poloxamers, typically added to stabilize mAb formulations, in lowering adsorption and aggregation of mAbs.

Our results establish a direct correspondence between the adsorption of mAbs at oil-water interfaces and aggregation, and the effect of surfactants in lowering aggregation by competitively adsorbing to these interfaces. These results can help in designing formulations better stabilized against aggregation at oil–water interfaces.