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Real-time estimation of bound water concentration during lyophilization with temperature-based state observers
Prakitr Srisuma1, George Barbastathis2, Richard D Braatz3
1Center for Computational Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
This study introduces a new method to accurately estimate bound water concentration during freeze-drying (lyophilization) secondary drying in real-time. This technique ensures biotherapeutic product quality by monitoring residual moisture without direct measurement.
Area of Science:
- Pharmaceutical Sciences
- Chemical Engineering
- Biotechnology
Background:
- Lyophilization (freeze-drying) enhances biotherapeutic stability, crucial for vaccines like mRNA COVID-19 vaccines.
- Accurate prediction of bound water concentration during secondary drying is essential for lyophilized product quality.
- Current methods lack real-time monitoring of bound water during this critical phase.
Purpose of the Study:
- To develop a novel technique for real-time estimation of bound water concentration during lyophilization's secondary drying stage.
- To ensure the quality and stability of lyophilized biotherapeutics by accurately monitoring residual moisture.
- To provide a framework applicable to other desorption-related processes.
Main Methods:
- Implementation of a state observer combining temperature measurements with mechanistic models of heat transfer and desorption kinetics.
- Utilizing a model-based approach that does not require online concentration measurements.
- Validation through both computational simulations and experimental data.
Main Results:
- The developed state observer accurately estimates bound water concentration in real-time across diverse conditions.
- The method demonstrates robustness against varying concentration levels, operating parameters, and measurement noise.
- Successful validation using both simulated and experimental lyophilization data.
Conclusions:
- The proposed state observer provides a reliable method for real-time bound water concentration estimation during lyophilization.
- This framework enhances the control and monitoring of residual moisture in lyophilized products.
- The technique's applicability extends to monitoring and controlling residual moisture in other desorption processes.
