WHITEPAPER - The Viscosity Reduction Platform: Viscosity-Reducing Excipients for Protein Formulation

Protein viscosity is one of the major obstacles in preparing highly concentrated protein formulations suitable for subcutaneous (subQ) injection. SubQ application of highly concentrated protein formulations enables a higher patient convenience and might thus lead to reduction in health costs. This can be achieved by reducing the time requirement of the patient to administer therapy, e.g. by enabling self-injection at home and reducing time required to do so. However, highly viscous protein solutions would require a significant force to be applied to the syringe for injection. As a result, the patient could experience a considerable amount of pain. In many cases, injectability would not be possible.1,2

When characterizing protein viscosity behavior, one can differentiate two different concentration regimes as shown in Figure 1. At concentrations below 75 mg/mL, proteins are rarely viscous. When increasing the concentration to between 100 and 200 mg/mL, some proteins exhibit elevated viscosity exceeding the limit of injectability, which
is typically between 20 and 25 mPas. At this concentration regime, several proteins exhibit an affinity for self-interaction, i.e. forming transient clusters that give rise to elevated viscosity. At concentrations above 200 mg/mL, the nearest neighbor distance between the protein molecules shrinks so that without a specific affinity for self-interactions, said protein-protein interactions take place. While viscosity-reducing excipients can affect proteins exhibiting either of these interaction patterns, they are likely to be more efficient at protein concentration regimes below 200 mg/mL.3,4