Viscosity Reduction of a Concentrated Monoclonal Antibody with Arginine·HCl and Arginine·Glutamate

To further advance a subcutaneous injection of monoclonal antibodies (mAbs) at elevated concentrations, novel concepts are needed to lower the viscosity. The addition of high concentrations of cosolutes, namely, arginine glutamate (Arg·Glu) or Arg·HCl, reduced the viscosity of a ∼250 mg/mL mAb solution up to 6-fold. With Arg·Glu, the viscosity of the mAb solution was reduced to 30 cP and for a polyclonal sheep IgG solution to 17 cP both at ∼250 mg/mL. Viscosities went through a maximum at the mAb isoelectric point for solutions with Arg·Glu or Arg·HCl. In contrast the viscosity was only weakly affected by NaCl or the preferentially excluded molecule trehalose. The large viscosity reduction from Arg may be attributed to direct binding to the mAb, resulting in suppression of both hydrophobic and local anisotropic electrostatic attraction. Aggregate formation was negligible for high cosolute mAb solutions as demonstrated by SEC even after 8 weeks of 25 °C storage.