New Model to Predict the Concentration-Dependent Viscosity of Monoclonal Antibody Solutions.

Concentrated monoclonal antibody solutions exhibit high solution viscosity, which is experimentally measured to be ∼1-2 orders of magnitude higher than the viscosity of water. However, physical processes responsible for the high antibody viscosity are not fully understood. We show that fluid occlusion due to the trapped solvent molecules within the boundaries formed by the aggregated antibodies is responsible for the elevated solution viscosity. We develop a theory to predict the viscosity of monoclonal antibodies based on the geometry of the antibody molecule and the aggregate morphology. We validate our theory with experiments and highlight useful insights obtained from the viscosity equation which could help in controlling the drug viscosity at the molecular design stage itself.