Specific interactions in high concentration antibody solutions resulting in high viscosity.
The purpose of this work was to investigate the self-associating behavior observed in high concentration monoclonal antibody (MAb1) solutions at pH 6.0. Zeta potential measurements over the pH range (4.0-9.0) showed lower net charges present on the molecule at pH 6.0 and 7.0. The point of zero charge or crossover from positive to negative potential was at pH 6.7 and was different from the theoretical isoelectric point (pI) of 7.8. Interaction parameter (k(D)) from dynamic light scattering (DLS) studies indicated that attractive interactions of a similar magnitude span over a pH range of 5.0-8.0. Change in k(D) values with increase in ionic strength corroborated that the interactions were electrostatic in origin. Comparative rheology analysis of three different monoclonal antibodies at pH 6.0, using ultrasonic shear rheometer, showed a high solution storage modulus (G') and its sharp increase in magnitude at high concentrations in MAb1. The shape of the rheology profile was indicative of strong attractive interactions between solute molecules. High specific attractive interactions may be attributed to charge-charge and charge-dipole interactions at the surface in the Fab regions of MAb1, and gives a reasonable explanation for the pH dependency of the rheological profile observed.
Yadav
Sandeep
S
Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut 06269, USA.
Liu
Jun
J
Shire
Steven J
SJ
Kalonia
Devendra S
DS
D000911:Antibodies, Monoclonal / Q000737:chemistry*; D004563:Electrochemistry; D006863:Hydrogen-Ion Concentration; D008027:Light; D009994:Osmolar Concentration; D019999:Pharmaceutical Solutions / Q000737:chemistry*; D025941:Protein Interaction Mapping / Q000379:methods*; D012212:Rheology / Q000379:methods*; D012542:Scattering, Radiation; D055672:Static Electricity; D013499:Surface Properties; D013816:Thermodynamics; D014783:Viscosity
D000911:Antibodies, Monoclonal; D019999:Pharmaceutical Solutions