Correlating multidimensional short-term empirical protein properties to long-term protein physical stability data via empirical phase diagrams
| Autor: | Jürgen Hubbuch, Marieke E. Klijn |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Time Factors
Surface Properties Computer science Drug Storage Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Stability (probability) 03 medical and health sciences 0302 clinical medicine Egg White Phase (matter) Animals Colloids Phase diagram Multidimensional analysis Protein Stability Proteins Function (mathematics) 021001 nanoscience & nanotechnology Term (time) Biopharmaceutical Muramidase 0210 nano-technology Biological system Reduction (mathematics) Chickens Hydrophobic and Hydrophilic Interactions |
| Zdroj: | International Journal of Pharmaceutics. 560:166-174 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2019.02.006 |
| Popis: | Identification of long-term stable biopharmaceutical formulations is essential for biopharmaceutical product development. Reduction of the number of long-term storage experiments and a well-defined formulation search space requires knowledge-based formulation screenings and a detailed protein phase behavior understanding. To achieve this, short-term analytical techniques can serve as predictors for long-term protein phase behavior. Protein phase behavior studies that investigate this concept commonly display shortcomings such as limited and small datasets, sample adjustments, or simplistic data analysis. To overcome these shortcomings, 150 unique lysozyme solutions were analyzed using six different short-term analytical techniques. Lysozyme’s structural properties, conformational stability, colloidal stability, surface charge, and surface hydrophobicity were obtained directly after formulation preparation. Employing the empirical phase diagram method, this short-term data was correlated to long-term physical stability data obtained during 40 days of storage. Short-term protein properties showed partial correlation to long-term phase behavior. Structural differences, changing surface properties, colloidal stability, and conformation stability as a function of formulation conditions were observed. This study contributes to long-term protein phase behavior research by presenting a systematic, data-dependent, and multidimensional data evaluation workflow to create a comprehensive overview of short-term protein analytics in relation to long-term protein phase behavior. |
| Databáze: | OpenAIRE |
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