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.
Keywords: Viscosity, arginine, antibody, immunoglobulin G, protein aggregation, serum albumin, molecular interaction.
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