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Studying Excipient Modulated Physical Stability and Viscosity of Monoclonal Antibody Formulations using Small-Angle Scattering

Published

Author(s)

Amy Yuanyuan Xu, Maria Monica Castellanos, Kevin Mattison, Joseph Curtis

Abstract

Excipients are a class of pharmacologically inert chemicals that are frequently added into concentrated therapeutic protein formulations for improved protein stability and reduced solutions viscosity. In concentrated protein formulations ,undesirable protein-protein interactions (PPI) can lead to protein aggregation and high solution viscosity, therefore, understanding the effects of excipients on the non-specific PPI is important for optimized formulation design. In this study, we used NIST monoclonal antibody (NISTmAb) reference material as the model antibody protein to examine the physical stability and vsicosity behavior of NISTmAb formulations with the presence of various excipients, varying in pH, salt composition and the presence of co-solutes like amino acids, sugars and surfactants. To this end, a wide range of high-throughput biophysical characterization techniques are used to obtain experimental parameters for better characterization of PPI and bulk solution viscosities of various formulations. Although no denaturation or aggregation was observed from all of the samples examined and that the net PPI appeared to repulsive in nature, detailed analysis of structure factor measured from SAXS revelaed that the use of ionic excipients such as pH and salts lead to increased short-ranged attraction, while the nonionic excipients including sugars, amino acids and polysorbate surfactants lead to increased repulsive PPI with increasing protein concentrations. The use of excipients lead to increased solution viscosity, especially at higher protein concentrations.
Citation
Molecular Pharmaceutics
Volume
16
Issue
10

Keywords

Protein, Aggregation, Colloidal Stability, Scattering

Citation

, A. , , M. , Mattison, K. and , J. (2019), Studying Excipient Modulated Physical Stability and Viscosity of Monoclonal Antibody Formulations using Small-Angle Scattering, Molecular Pharmaceutics, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=927122 (Accessed March 3, 2024)
Created October 6, 2019, Updated September 12, 2020