Second osmotic virial coefficients of therapeutic proteins in the presence of excipient-mixtures can be predicted to aid an efficient formulation design
| Autor: | David Teschner, Christoph Brandenbusch, Gabriele Sadowski, Miko Schleinitz |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Molecular interactions
Aqueous solution Chemistry Excipient 02 engineering and technology 010402 general chemistry 021001 nanoscience & nanotechnology Condensed Matter Physics 01 natural sciences Atomic and Molecular Physics and Optics 0104 chemical sciences Electronic Optical and Magnetic Materials Virial coefficient Solubilization Materials Chemistry medicine Screening method Physical and Theoretical Chemistry 0210 nano-technology Biological system Spectroscopy medicine.drug |
| Zdroj: | Journal of Molecular Liquids. 283:575-583 |
| ISSN: | 0167-7322 |
| Popis: | Early- and late-stage formulation development for biopharmaceuticals (e.g. therapeutic proteins) remains a challenging task, especially when one has to select suitable excipients to solubilize and stabilize the protein in solution. State-of-the-art formulation development includes cost-intensive high-throughput screening methods to identify suitable excipients and formulation conditions. These methods often deliver a “working” formulation but unlikely the “optimal” formulation. Within this work, we developed a novel method that allows identifying suitable excipients based on the second osmotic virial coefficient B22 as the measure of choice for protein-protein interactions in aqueous solution in the presence of excipients (salts, sugars, amino acids, etc.). B22 is easily accessible by light scattering methods and advanced thermodynamic models like the extended mxDLVO model. Aqueous immunoglobulin G solutions including sugars, amino acids, surfactants and salts as excipients were used as model systems within this work. Applying the extended mxDLVO, the model allows predicting protein-protein interactions with high accuracy for mixtures of up to three excipients in one formulation. These measurements allow for quick identification of suitable excipients and their concentrations and are giving a greater insight in molecular interactions under the respective formulation conditions. An application of this method in future formulation development has the potential to reduce time-consuming and cost-intensive screening methods and finally lead to optimal formulations. |
| Databáze: | OpenAIRE |
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