Viscosity Behavior of High-Concentration Protein Mixtures

Highly concentrated protein solutions are becoming increasingly commonplace within the biopharmaceutical industry as more products are developed that feature high doses of drug intended for subcutaneous administration. An as-yet undeveloped subclass of these products feature multiple proteins coformulated together in high-concentration protein mixtures. Previous work has illustrated that the viscosity of aqueous solutions of various proteins at high concentrations can be remarkably different across otherwise similar molecules. This work characterizes the viscosity behavior of mixtures of such proteins, primarily monoclonal antibodies, and shows that a simple mixing rule first proposed by Arrhenius predicts the viscosity of an arbitrary mixture. This approach is shown to successfully calculate the viscosity of mixtures of proteins ranging up to 250 mg/mL total protein concentration and approximately 1700 cP at different ionic strengths and with accuracy errors of less than 10%. Only information about the viscosity of the isolated protein components of the mixture is required for the calculations.