Viscosity Control of Protein Solution by Small Solutes: A Review

Viscosity of protein solution is one of the most troublesome issues for the high-concentration formulation of protein drugs. In this review, we summarize the practical methods that suppress the viscosity of protein solution using small molecular additives. The small amount of salts decreases the viscosity that results from electrostatic repulsion and attraction. The chaotrope suppresses the hydrophobic attraction and cluster formation, which can lower the solution viscosity. Arginine hydrochloride (ArgHCl) also suppresses the solution viscosity due to the hydrophobic and aromatic interactions between protein molecules. The small molecular additives are the simplest resolution of the high viscosity of protein solution as well as understanding of the primary cause in complex phenomena of protein interactions.