title: Do clustering monoclonal antibody solutions really have a concentration dependence of viscosity?
abstract: Protein solution rheology data in the biophysics literature have incompletely identified factors that govern hydrodynamics. Whereas spontaneous protein adsorption at the air/water (A/W) interface increases the apparent viscosity of surfactant-free globular protein solutions, it is demonstrated here that irreversible clusters also increase system viscosity in the zero shear limit. Solution rheology measured with double gap geometry in a stress-controlled rheometer on a surfactant-free Immunoglobulin solution demonstrated that both irreversible clusters and the A/W interface increased the apparent low shear rate viscosity. Interfacial shear rheology data showed that the A/W interface yields, i.e., shows solid-like behavior. The A/W interface contribution was smaller, yet nonnegligible, in double gap compared to cone-plate geometry. Apparent nonmonotonic composition dependence of viscosity at low shear rates due to irreversible (nonequilibrium) clusters was resolved by filtration to recover a monotonically increasing viscosity-concentration curve, as expected. Although smaller equilibrium clusters also existed, their size and effective volume fraction were unaffected by filtration, rendering their contribution to viscosity invariant. Surfactant-free antibody systems containing clusters have complex hydrodynamic response, reflecting distinct bulk and interface-adsorbed protein as well as irreversible cluster contributions. Literature models for solution viscosity lack the appropriate physics to describe the bulk shear viscosity of unstable surfactant-free antibody solutions.
authors: Formulations Sciences Department, MedImmune, Gaithersburg, MD, USA. pathakj@medimmune.com
authors: Jai A
authors: JA
authors: Pathak
authors: Rumi R
authors: RR
authors: Sologuren
authors: Rojaramani
authors: R
authors: Narwal
mesh_terms: D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry*; D012212:Rheology; D012996:Solutions; D014783:Viscosity
chemical_list: D007074:Immunoglobulin G; D012996:Solutions