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Water Activity as an Indicator for Antibody Storage Stability in Lyophilized Formulations.
Maximilian Zäh1, Christoph Brandenbusch1, Sebastian Groël2
1Laboratory of Thermodynamics, Department of Biochemical and Chemical Engineering, TU Dortmund University, Emil-Figge-Street 70, Dortmund 44227, Germany.
Molecular Pharmaceutics
|January 14, 2025
Summary
This study introduces a new method for creating stable lyophilized biopharmaceuticals by using water activity and glass-transition temperature. This approach helps predict excipient combinations for long-term drug stability.
Area of Science:
- Pharmaceutical Science
- Biotechnology
- Materials Science
Background:
- Lyophilization is crucial for biopharmaceutical preservation, traditionally explained by vitrification and water replacement.
- Existing methods rely on empirical approaches for formulation development.
- Sensitive biologics like monoclonal antibodies require robust stabilization strategies.
Purpose of the Study:
- To propose a novel predictive strategy for lyophilized formulation stability.
- To integrate water activity and glass-transition temperature (Tg) as key stability indicators.
- To identify optimal excipient combinations for enhanced biopharmaceutical stability.
Main Methods:
- Calculated water activity using activity coefficient and residual water content.
- Employed the perturbed-chain statistical association fluid theory (PC-SAFT) model for activity coefficient predictions.
- Utilized the Gordon-Taylor equation to calculate glass-transition temperature (Tg).
- Validated the predictive model with experimental stability studies.
Main Results:
- Identified sucrose/ectoine mixtures as a favorable excipient system.
- Determined that a water activity range of 0.025–0.25 correlates with high long-term stability.
- Demonstrated the ability to achieve favorable water activity with low residual moisture and high Tg.
- Established formulation windows offering broad stability ranges.
Conclusions:
- The proposed model advances biopharmaceutical formulation development beyond traditional empirical methods.
- Integrating water-excipient interactions and residual moisture provides a robust predictive pathway.
- This approach enables the rational design of stable lyophilized biopharmaceutical formulations.
