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A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
Published on: August 9, 2022
Determining antibody stability: creation of solid-liquid interfacial effects within a high shear environment
James G Biddlecombe1, Alan V Craig, Hu Zhang
1The Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK.
Biotechnology Progress
|August 25, 2007
Summary
High shear stress at solid-liquid interfaces significantly aggregates proteins, like monoclonal IgG4 antibodies. Understanding and minimizing these shear environments is crucial for stable protein formulation development.
Area of Science:
- Biopharmaceutical science
- Chemical engineering
- Protein chemistry
Background:
- Protein formulations are susceptible to aggregation and precipitation under stress.
- Controlling shear stress at solid-liquid interfaces is critical for bioprocessing.
- Existing methods for assessing shear stress effects on proteins are limited.
Purpose of the Study:
- To evaluate protein formulation stability under defined shear conditions at a solid-liquid interface.
- To develop and utilize a novel device for generating quantifiable shear rates.
- To investigate the impact of high shear strain rates on monoclonal IgG4 stability.
Main Methods:
- Development of a rotating disk device to generate controlled shear strain rates (up to 3.4 x 10(4) s(-1)).
- Exclusion of air-liquid interfaces and precise temperature control within the device.
- Computational fluid dynamics (CFD) to model fluid flow and determine shear rates.
- Monitoring of monomeric antibody concentration (gel permeation HPLC) and aggregation (turbidity at 350 nm).
Main Results:
- High shear strain rates induced significant protein aggregation and precipitation.
- Monomeric antibody concentration reduction followed first-order kinetics.
- The rate of monomer reduction exhibited a nonlinear relationship with shear strain rate.
Conclusions:
- Solid-liquid interface shear stress is a critical factor in protein aggregation.
- The developed device provides a quantifiable method for assessing shear-induced protein degradation.
- Minimizing high shear environments during protein processing is essential for maintaining formulation stability.
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