Prediction of colloidal stability of high concentration protein formulations

Abstract

A major aspect determining the colloidal properties of proteins in solution is the interaction between them and with surrounding molecules. These interactions can be described by the concentration dependency of the protein diffusivity (k_D), as derived by dynamic light scattering and was determined for different solutions of monoclonal antibodies varying in pH, ionic strength and presence/absence of co-solute(s). Concerning colloidal stability, protein solutions of different k_D values are evaluated, based on their initial solution opalescence, to assess protein association. The current investigation shows that solution conditions with large k_D values, indicating high repulsive protein–protein interactions, show lower initial opalescence, compared to solution conditions with low k_D values. Upon applying stirring stress, to assess colloidal stability, the trend is such that, the higher k_D values are, the more stable the protein solutions are, as long as the thermodynamic and conformational stability is not impaired. Besides, k_D allows ranking of solution conditions for highly concentrated immunoglobulin solutions up to concentrations of ～200?mg?mL^?1 with regard to protein self-association and thus opalescent properties. The present study shows that the protein interaction parameter k_D can be used as a surrogate parameter for a qualitative prediction of protein association and, thus, colloidal protein stability.