Polysorbate identity and quantity dictates 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 high-concentration formulations. Here, the
extensional flow properties of protein-excipient solutions are examined
via dripping-onto-substrate (DoS) extensional rheology, using a model
ovalbumin protein (OVA) 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 solution concentrations where surface tension differences
drive changes in extensional flow behavior, and at small PS:OVA ratios,
which impacts the onset of weakly elastic behavior. Undesirable
elasticity is observed in ultra-concentrated formulations, independent
of PS identity; higher PS contents are required to observe these effects
than with 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.