Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 95, Issue 9, Pages 1967-1983Publisher
JOHN WILEY & SONS INC
DOI: 10.1002/jps.20663
Keywords
protein; protein formulation; protein-protein interactions; stability; monoclonal antibody; IgG(2); high protein concentration solutions; complex viscosity; storage modulus; ultrasonic shear rheometer
Ask authors/readers for more resources
The purpose of this work was to explore the utilization of high-frequency rheology analysis for assessing protein-protein interactions in high protein concentration solutions. Rheology analysis of a model monoclonal immunoglobulin G(2) solutions was conducted on indigenously developed ultrasonic shear rheometer at frequency of 10 MHz. Solutions at pH 9.0 behaved as most viscous and viscoelastic whereas those at pH 4.0 and 5.4 exhibited lower viscosity and viscoelasticity, respectively. Intrinsic viscosity, hydrophobicity, and conformational analysis could not account for the rheological behavior of IgG(2) solutions. Zeta potential and light scattering measurements showed the significance of electroviscous and specific protein-protein interactions in governing rheology of IgG(2) solutions. Specific protein-protein interactions resulted in formation of reversible higher order species of monomer. Solution storage modulus (G'), and not loss modulus or complex viscosity, was the more reliable parameter for predicting protein-protein interactions. Predictions about the nature of protein-protein interactions made on the basis of solution G' were found to be consistent with observed effect of pH and ionic strength on zeta potential and scattered intensity of IgG(2) solutions. Results demonstrated the potential of high-frequency storage modulus measurements for understanding behavior of proteins in solutions and predicting the nature of protein-protein interactions. (c) 2006 Wiley-Liss, Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available