Viscoelastic characterization of high concentration antibody formulations using quartz crystal microbalance with dissipation monitoring.

Full Abstract

With increasing protein concentrations, therapeutic protein formulations are increasingly demonstrating significant deviations from ideal dilute solution behavior due to protein-protein interactions. These interactions lead to unique biophysical challenges in the administration of biopharmaceuticals including high apparent viscosity and viscoelasticity as well as challenges in maintaining the physical stability of proteins in solution. Here, we describe a straightforward analytical method to calculate the complex modulus and viscosity of high concentration protein solutions from measurements made using quartz crystal microbalance with dissipation monitoring (QCM-D). Further, this methodology was used to investigate the dependence of the storage and loss moduli (G' and G'', respectively) of a humanized monoclonal antibody solution on solution pH. Unlike recent reports, the effect of protein deposition onto the surface of the quartz sensor crystal was measured and explicitly accounted for during analysis when determining the solution's complex modulus. It was found that the ratio G''/G' was significantly greater than unity for all solutions investigated, but demonstrated a distinct maximum at pH 5.5 indicating that the solution exhibited the greatest liquid-like behavior at this pH. In addition, measurements were made at higher frequencies, which were found to be more sensitive to the changes in pH than those made at lower frequencies. It was also found that the viscoelastic ratio was relatively insensitive to the frequency of measurement at lower pH, but showed greater dependence on frequency as pH increased. The characterization of the rheological properties of high concentration antibody solutions provides insight into protein-protein interactions, and the methodology presented here demonstrates a straightforward way to determine the viscoelastic properties using ultrasonic rheology without the drawbacks of numerical fitting.

Author information

Author/s: Patel, Ankit R (AR); Kerwin, Bruce A (BA); Kanapuram, Sekhar R (SR);

Affiliation: Department of Chemical Engineering, Stanford University, Stanford, California 94305, USA.

Journal and publication information

Publication Type: Journal Article

Journal: Journal of pharmaceutical sciences (J Pharm Sci), published in United States. (Language: eng)

Reference: 2009-Sep; vol 98 (issue 9) : pp 3108-16

Dates: Created 2009/08/04; Completed 2009/10/12;

PMID: 19025898, status: MEDLINE (last retrieval date: 10/12/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.