Interfacial Pressure and Viscoelasticity of Antibodies and Their Correlation to Long-Term Stability in Formulation.

Monoclonal antibodies (mAbs) form viscoelastic gel-like layers at the air-water interface due to their amphiphilic nature, and this same protein characteristic can lead to undesired aggregation of proteins in therapeutic formulations. We hypothesize that the interfacial viscoelasticity and surface pressure of mAbs at the air-water interface will correlate with their long-term stability. To test this hypothesis, the interfacial viscoelastic rheology and surface pressure of five different antibodies with varying visible particle counts from a three-year stability study were measured. We find that both the surface pressures and interfacial elastic moduli correlate well with the long-time mAb solution stability within a class of mAbs with the interfacial elastic moduli being particularly sensitive to discriminate between stable and unstable mAbs across a range of formulations. Furthermore, X-ray reflectivity was used to gain insight into the interfacial structure of mAbs at the air-water interface, providing a possible molecular mechanism to explain the relationship between interfacial elastic moduli and the long-term stability.