Version 1
: Received: 3 July 2024 / Approved: 3 July 2024 / Online: 3 July 2024 (08:51:18 CEST)
How to cite:
Arakawa, T.; Nishinami, S.; Shiraki, K.; Tomioka, Y.; Akuta, T. Inter-molecular Interactions of High Concentration Antibody Formulation Resulting in Problems of Viscosity, Opalescence and Phase Separation. Preprints2024, 2024070325. https://doi.org/10.20944/preprints202407.0325.v1
Arakawa, T.; Nishinami, S.; Shiraki, K.; Tomioka, Y.; Akuta, T. Inter-molecular Interactions of High Concentration Antibody Formulation Resulting in Problems of Viscosity, Opalescence and Phase Separation. Preprints 2024, 2024070325. https://doi.org/10.20944/preprints202407.0325.v1
Arakawa, T.; Nishinami, S.; Shiraki, K.; Tomioka, Y.; Akuta, T. Inter-molecular Interactions of High Concentration Antibody Formulation Resulting in Problems of Viscosity, Opalescence and Phase Separation. Preprints2024, 2024070325. https://doi.org/10.20944/preprints202407.0325.v1
APA Style
Arakawa, T., Nishinami, S., Shiraki, K., Tomioka, Y., & Akuta, T. (2024). Inter-molecular Interactions of High Concentration Antibody Formulation Resulting in Problems of Viscosity, Opalescence and Phase Separation. Preprints. https://doi.org/10.20944/preprints202407.0325.v1
Chicago/Turabian Style
Arakawa, T., Yui Tomioka and Teruo Akuta. 2024 "Inter-molecular Interactions of High Concentration Antibody Formulation Resulting in Problems of Viscosity, Opalescence and Phase Separation" Preprints. https://doi.org/10.20944/preprints202407.0325.v1
Abstract
Abstract: Currently, antibodies are major therapeutic modalities in biopharmaceutical research and development. Because of required high dose for certain clinical applications, antibodies are formulated at high protein concentration for convenience of administration, shipping and storage. We will describe the inter-molecular interactions that can occur in such a crowded environment of high protein concentration. Two types of repulsive interactions, i.e., electrostatic and excluded volume effects, and three types of attractive interactions, i.e., hydrophobic, electrostatic and cross-linking, need to be considered in such a crowded environments. We then show consequences of such inter-molecular interactions, leading to high viscosity, opalescence and phase separation of antibody solutions. Co-solvents are used to control the stability, structure and molecular interactions and thereby to alleviate these solution problems. Among various co-solvents, arginine has been extensively used to suppress protein-protein interactions at high protein concentration. Arginine weakly but extensively interacts with aromatic/hydrophobic groups as well as charged groups on proteins, leading to effective suppression of viscosity, opalescence and phase separation of antibody solution.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
