Interfacial Pressure and Viscoelasticity of Antibodies and Their Correlation to Long-Term Stability in Formulation

Published

November 2, 2023

Author(s)

Kiet Pham, Benjamin Thompson, Tingting Wang, Shayak Samaddar, Ken Qian, Yun Liu, Norman Wagner

Abstract

Monoclonal antibodies (mAbs) form viscoelastic gel-like layers at the air−water interface due to their amphiphilic nature, and this same protein characteristic can lead to undesired aggregation of proteins in therapeutic formulations. We hypothesize that the interfacial viscoelasticity and surface pressure of mAbs at the air−water interface will correlate with their long-term stability. To test this hypothesis, the interfacial viscoelastic rheology and surface pressure of five different antibodies with varying visible particle counts from a three-year stability study were measured. We find that both the surface pressures and interfacial elastic moduli correlate well with the long-time mAb solution stability within a class of mAbs with the interfacial elastic moduli being particularly sensitive to discriminate between stable and unstable mAbs across a range of formulations. Furthermore, X-ray reflectivity was used to gain insight into the interfacial structure of mAbs at the air−water interface, providing a possible molecular mechanism to explain the relationship between interfacial elastic moduli and the long-term stability.

Citation

Journal of Physical Chemistry B

Volume

127

Issue

45

Pub Type

Journals

Download Paper

https://doi.org/10.1021/acs.jpcb.3c05900

Local Download

Keywords

protein, stability, interfacial, rheology, air-water interface

Citation

Pham, K. , Thompson, B. , Wang, T. , Samaddar, S. , Qian, K. , Liu, Y. and Wagner, N. (2023), Interfacial Pressure and Viscoelasticity of Antibodies and Their Correlation to Long-Term Stability in Formulation, Journal of Physical Chemistry B, [online], https://doi.org/10.1021/acs.jpcb.3c05900, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=956457 (Accessed December 11, 2024)