(753f) Stability of Monoclonal Antibody Solutions Subject to Expansion/Compression Cycles at the Air/Water Interface

The specificity of monoclonal antibodies for their target antigens underpins their efficacy in targeting debilitating conditions in human health. The interfacial hydrodynamic stresses encountered by monoclonal antibodies under typical manufacturing, filling and shipping conditions may also induce and/or accelerate partial unfolding and sub-visible particle formation that can compromise their efficacy and safety during administration to the patient. We demonstrate that dilatational surface deformations are more detrimental to antibody stability when compared to constant-area shear of the air-water interface. We have constructed a dilatational interfacial rheometer that utilizes orthogonal methods of pressure and curvature measurements to study the interfacial viscoelasticity vis a vis protein stability under interfacial aging. Dilatation measurements of the stress response to small and large-amplitude oscillatory frequency sweeps and stress-relaxation experiments are used to understand the relaxation timescales that describe the adsorbed interfacial film such as the processes of partial unfolding, aggregation, and particle shedding. We find data that suggest irreversibly adsorbed proteins may be ejected from the air/water interface only when the bubble is deflated faster than the timescale of surface structural rearrangement. These rheological studies frame a molecular understanding of the protein-protein interactions at the complex-fluid interface.