Beyond glass transitions: studying the highly viscous and elastic behavior of frozen protein formulations using low temperature rheology and its potential implications on protein stability
| Autor: | Tian Wu, Priti Baker, Beekman Alice C, M. D. Hale, Michael Eschenberg, Merrill Seymour Goldenberg, Deirdre Murphy Piedmonte, Jian Hua Gu |
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| Rok vydání: | 2012 |
| Předmět: |
Phase transition
Sucrose Materials science Pharmaceutical Science Thermodynamics Viscoelastic Substances Instability Phase Transition Excipients Viscosity Protein stability Rheology Phase (matter) Freezing Pharmacology (medical) Elasticity (economics) Pharmacology Quantitative Biology::Biomolecules Protein Stability Organic Chemistry Elasticity Condensed Matter::Soft Condensed Matter Immunoglobulin G Molecular Medicine Glass transition Biotechnology |
| Zdroj: | Pharmaceutical research. 30(2) |
| ISSN: | 1573-904X |
| Popis: | A novel application of oscillatory shear rheology was used to directly monitor global phase behavior of protein formulations in the frozen state and study its correlation with physical instability of frozen protein formulations.Oscillatory rheology was used to measure changes in rheological parameters and to identify mechanical softening temperature (Ts*) and related properties of an IgG2 mAb formulation. Rheological measurements were compared to DSC/MDSC. Physical stability of IgG2 formulations was monitored by SE-HPLC.Rheological parameters and Ts* of an IgG2 formulation were sensitive to physical/morphological phase changes during freezing and thawing. Ts* of the frozen formulation was a function of concentration of protein and excipient. Complex modulus, G*, and phase angle, δ, for IgG2 at 70 mg/mL in a sucrose-containing formulation showed the system was not completely frozen at -10°C, which correlated to stability data consistent with ice-induced protein aggregation.We report the first application of oscillatory shear rheology to study phase behavior of IgG2 in a sucrose-containing formulation and its correspondence with physical stability not explained by glass transition (Tg'). We provide a mechanism and data suggesting that protein instability occurs at the ice/water interface. |
| Databáze: | OpenAIRE |
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