Polysorbate identity and quantity dictate the extensional flow properties of protein‐excipient solutions

Abstract

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.

Pinching dynamics, extensional rheology, and stringiness of saliva substitutes

“…Unlike CaBER or Trimaster or FISER, the DoS protocols involve no moving parts and therefore, allow analysis of low viscosity and low elasticity fluids as the same interplay of stresses that is relevant for jetting, CaBER or dripping drives capillarity-driven pinching dynamics in DoS rheometry. The robustness and utility of this frugal technique has resulted in its increasing use for studying the extensional rheology response of polymer solutions and macromolecular biological fluids, 88,89,153,154,[171][172][173][174][175][176][177] but a thorough examination of the influence of interfacial rheology, complexation between polymers and other ingredients, and adsorption kinetics are also warranted.…”