Effects of anion excipients on the viscosity of high-concentration mAb solution.

High protein concentrations often lead to high viscosity, necessitating reduced solution viscosity. We investigated the effects of eight anionic excipients commonly used in biopharmaceutical formulations on the solution viscosity of high-concentration monoclonal antibodies using three antibodies with different isoelectric points. The three antibodies exhibited attractive or repulsive protein-protein interaction tendencies in histidine buffer without anionic excipients. The effect of adding anionic excipients on solution viscosity differed by interaction tendencies. Preferential interaction coefficients revealed differences in the extent of interaction between individual anionic excipients and antibodies. Comparison with chloride, positioned in the middle of the Hofmeister series, suggested that the observed viscosity behavior could only be partially explained by the previously reported Hofmeister anion effects on solution viscosity. We examined the effects of combining L-arginine with each anionic excipient as a counter anion. Formulations containing L-arginine and other anionic excipients contributed more strongly to reducing solution viscosity than L-arginine hydrochloride. The effects of anionic excipients on viscosity can be understood in terms of protein-protein interactions of an antibody in the presence of anionic excipients; whether anionic excipients strengthen or weaken the intrinsic protein-protein interactions is important, underscoring the key indicator for selecting the optimal anionic excipients when designing high-concentration formulations with lower viscosities.