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

Autor: Miko Schleinitz, Christoph Brandenbusch, Gabriele Sadowski
Rok vydání: 2019
Předmět:
Zdroj: International journal of pharmaceutics. 569
ISSN: 1873-3476
Popis: 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 B22 which can be measured using static light scattering techniques. Furthermore B22 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 B22-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 B22 allows to quickly identify a first guess on suitable formulation conditions that then can be further evaluated with existing methods/knowledge.
Databáze: OpenAIRE
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