Viscosity behavior of high-concentration protein mixtures

Area of Science:

• Biopharmaceutical development
• Protein formulation science
• Physical chemistry of solutions

Background:

• Highly concentrated protein solutions are prevalent in the biopharmaceutical industry for high-dose subcutaneous drug products.
• Coformulating multiple proteins in high-concentration mixtures presents unique formulation challenges.
• Protein solution viscosity can vary significantly even among similar molecules at high concentrations.

Purpose of the Study:

• To characterize the viscosity behavior of high-concentration protein mixtures, particularly those containing monoclonal antibodies.
• To evaluate the applicability of established mixing rules for predicting the viscosity of multi-protein formulations.
• To establish a predictive model for viscosity in complex protein mixtures relevant to biopharmaceutical development.

Main Methods:

• Investigated viscosity of individual protein solutions and their mixtures at high concentrations (up to 250 mg/mL).
• Applied the Arrhenius-based mixing rule to predict the viscosity of arbitrary protein mixtures.
• Validated predictive model accuracy across varying ionic strengths and protein compositions.

Main Results:

• The Arrhenius mixing rule accurately predicts the viscosity of high-concentration protein mixtures.
• The model demonstrated less than 10% error in viscosity calculations for mixtures up to 250 mg/mL and ~1700 cP.
• Accurate predictions were achieved using only the viscosity data of the individual protein components.

Conclusions:

• A simple Arrhenius-based mixing rule effectively predicts the viscosity of complex, high-concentration protein mixtures.
• This predictive capability simplifies formulation development for multi-protein biopharmaceuticals.
• The findings offer a valuable tool for optimizing subcutaneous drug product development.