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Intermolecular Interactions and the Viscosity of Highly Concentrated Monoclonal Antibody Solutions

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The large increase in viscosity of highly concentrated monoclonal antibody solutions can be challenging for downstream processing, drug formulation, and delivery steps. The objective of this work was to examine the viscosity of highly concentrated solutions of a high purity IgG1 monoclonal antibody over a wide range of protein concentrations, solution pH, ionic strength, and in the presence / absence of different excipients.


Experiments were performed with an IgG1 monoclonal antibody provided by Amgen. The steady-state viscosity was evaluated using a Rheometrics strain-controlled rotational rheometer with a concentric cylinder geometry.


The viscosity data were well-described by the Mooney equation. The data were analyzed in terms of the antibody virial coefficients obtained from osmotic pressure data evaluated under the same conditions. The viscosity coefficient in the absence of excipients was well correlated with the third osmotic virial coefficient, which has a negative value (corresponding to short range attractive interactions) at the pH and ionic strength examined in this work.


These results provide important insights into the effects of intermolecular protein-protein interactions on the behavior of highly concentrated antibody solutions.

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Bovine serum albumin


Immunoglobulin G


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The authors would like to acknowledge Amgen, Inc. for donation of the monoclonal antibody and for their financial support. The authors would also like to thank Dr. Ralph Colby in the Department of Materials Science and Engineering at Penn State for use of the RFS II Rheometrics Fluids Spectrometer.

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Correspondence to Andrew L Zydney.

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Binabaji, E., Ma, J. & Zydney, A.L. Intermolecular Interactions and the Viscosity of Highly Concentrated Monoclonal Antibody Solutions. Pharm Res 32, 3102–3109 (2015).

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