Application Note: Investigating Metastability: Injectability of Aged Protein Solutions

Protein formulations are thermodynamically metastable, which means the measurable characteristics of these solutions change over time. One such characteristic that is important for injectable protein formulations is viscosity. The viscosity of a protein solution has a direct impact on the injection force or injectability of the solution. For injectability, metastability means that the force required to deliver the protein formulation will change as the formulation ages.

In this application note, we monitored protein viscosity as a function of time for two formulations, one with excess sodium chloride and one with arginine-HCl. We then calculated the injection force of the formulation as a function of shear rate and needle size at each time point and quantified the change. We found that the injection force of these formulations increases with age, however the formulation with excess sodium chloride had a much larger increase in injection force than the formulation with arginine-HCl. The implications of these results suggest that monitoring viscosity as injectable protein solutions age is vital for understanding how they will behave in the time between formulation and delivery.