Protein-protein interactions and water activity coefficients can be used to aid a first excipient choice in protein formulations.

Autor: Schleinitz M; Laboratory of Thermodynamics, Department of Biochemical and Chemical Engineering, Emil-Figge-Str. 70, 44227 Dortmund, Germany., Sadowski G; Laboratory of Thermodynamics, Department of Biochemical and Chemical Engineering, Emil-Figge-Str. 70, 44227 Dortmund, Germany., Brandenbusch C; Laboratory of Thermodynamics, Department of Biochemical and Chemical Engineering, Emil-Figge-Str. 70, 44227 Dortmund, Germany. Electronic address: christoph.brandenbusch@tu-dortmund.de.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2019 Oct 05; Vol. 569, pp. 118608. Date of Electronic Publication: 2019 Aug 12.
DOI: 10.1016/j.ijpharm.2019.118608
Abstrakt: With respect to all biopharmaceuticals marketed to date, monoclonal antibodies represent the largest fraction with more than 48% market share (2012). However, the development of biopharmaceutical formulations is a challenging task, and time-consuming and cost-intensive high-throughput screenings are still state-of-the-art in formulation design. These screening techniques are almost exclusively based on heuristic decisions thus the benefit in terms of mechanistic understanding is often unclear. It requires novel, physical-sound methods to enhance/optimize future formulation development, ideally by understanding molecular interactions in these complex solutions. A suitable and evaluated measure-of-choice to characterize protein-protein interactions in aqueous protein solutions is the second osmotic virial coefficient B 22 which can be measured using static light scattering techniques. Furthermore B 22 can be modeled/predicted via the extended mxDLVO model for protein-protein interactions in the presence of single excipients and excipient-mixtures. Building up on this approach, giving an additional insight into water-water and water-excipient interactions, the thermodynamic equation-of-state ePC-SAFT is used to calculate water activity coefficients in the presence of excipient-mixtures. Immunoglobulin G (IgG) was chosen as a model protein to predict B 22 -values for IgG in the presence of model excipient-mixtures (trehalose-NaCl, l-histidine-trehalose, l-histidine-NaCl). The combination of water activity coefficients and B 22 allows to quickly identify a first guess on suitable formulation conditions that then can be further evaluated with existing methods/knowledge.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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