Limited studies measure extensional rheology in protein solutions due to volume constraints and measurement challenges. We developed a small-volume, Dripping-onto-Substrate (DoS) extensional rheology device to measure the capillary thinning of...

While protein medications are promising for treatment of cancer and autoimmune diseases, challenges persist in terms of development and injection stability of highconcentration formulations. Here, the extensional flow properties of proteinexcipient solutions are examined via dripping-onto-substrate extensional rheology, using a model ovalbumin (OVA) protein and biocompatible excipients polysorbate 20 (PS20) and 80 (PS80). Despite similar PS structures, differences in extensional flow are observed based on PS identity in two regimes: at moderate total concentrations where surface tension differences drive changes in extensional flow behavior, and at small PS:OVA ratios, which impact the onset of weakly elastic flow behavior.Undesirable elasticity is observed in ultra-concentrated formulations, independent of PS identity; higher PS contents are required to observe these effects than in analogous polymeric excipient solutions. These studies reveal novel extensional flow behaviors in protein-excipient solutions, and provide a straightforward methodology for assessing the extensional flow stability of new protein-excipient formulations.