A new mathematical model for monitoring the temporal evolution of the ice crystal size distribution during freezing in pharmaceutical solutions
Name
Colucci_EurJPharmBiopharm_2020.pdf
Description
Submitted version
Size
1.68 MB
Format
Unknown
Checksum (MD5)
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Author(s)
Colucci, Domenico
Fissore, Davide
Barresi, Antonello A.
Braatz, Richard D.
Date Issued
March 2020
Journal
European Journal of Pharmaceutics and Biopharmaceutics
Publisher
Elsevier BV
Version
Original manuscript
Abstract
© 2020 Elsevier B.V. The freezing step plays a key role in the overall economy of the vacuum freeze-drying of pharmaceuticals, since the nucleation and crystal growth kinetics determine the number and size distribution of the crystals formed. In this work, a new mathematical model of the freezing step of a (bio)pharmaceutical solution is developed and validated. Both nucleation and crystal growth kinetics are modeled and included in a one-dimensional population balance (1D-PBM) that describes, given the product temperature measurement, the evolution of the pore size distribution during freezing. The developed model is coupled with the real-time measurements obtained from an infrared video camera. The ending time of the primary drying stage, and the maximum temperature inside the material, simulated through a simplified model of the process and the pore distribution forecast, resulted in good agreement with experimental values. The resulting Process Analytical Technology (PAT) has the potential to boost the development and optimization of a freeze-drying cycle and the implementation of a physically grounded Quality-by-Design approach in the manufacturing of pharmaceuticals. A more general mathematical model, including the aforementioned population balance, of a vial filled with a solution of sucrose was also developed and used to further validate the approach.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.ejpb.2020.01.004
