Real-time estimation of bound water concentration during lyophilization with temperature-based state observers
Name
2407.13844v2.pdf
Description
Accepted version
Size
4.9 MB
Format
Adobe PDF
Checksum (MD5)
0d14792a3ff3e770ca3200365254ed04
Author(s)
Srisuma, Prakitr
Barbastathis, George
Braatz, Richard D
Date Issued
November 2024
Journal
International Journal of Pharmaceutics
Publisher
Elsevier BV
Citation
Srisuma, Prakitr, Barbastathis, George and Braatz, Richard D. 2024. "Real-time estimation of bound water concentration during lyophilization with temperature-based state observers." International Journal of Pharmaceutics, 665.
Version
Author's final manuscript
Abstract
Lyophilization (aka freeze drying) has been shown to provide long-term stability for many crucial biotherapeutics, e.g., mRNA vaccines for COVID-19, allowing for higher storage temperature. The final stage of lyophilization, namely secondary drying, entails bound water removal via desorption, in which accurate prediction of bound water concentration is vital to ensuring the quality of the lyophilized product. This article proposes a novel technique for real-time estimation of the bound water concentration during secondary drying in lyophilization. A state observer is employed, which combines temperature measurement and mechanistic understanding of heat transfer and desorption kinetics, without requiring any online concentration measurement. Results from both simulations and experimental data show that the observer can accurately estimate the concentration of bound water in real time for all possible concentration levels, operating conditions, and measurement noise. This framework can also be applied for monitoring and control of the residual moisture in other desorption-related processes.
MIT Department
Massachusetts Institute of Technology. Center for Computational Science and Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Creative Commons Attribution-Noncommercial-ShareAlike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.ijpharm.2024.124693
