LAPSE:2023.35965
Published Article
LAPSE:2023.35965
Effect of the Freezing Step on Primary Drying Experiments and Simulation of Lyophilization Processes
June 7, 2023
Lyophilization is a widely used preservation method for thermosensitive products. It consists of three process steps: freezing, primary and secondary drying. One of the major drawbacks is the long processing time. The main optimization effort was put into the primary drying phase since it is usually the longest phase. However, the freezing step is of immense importance for process efficiency and product quality. The lack of control during freezing comprises a challenge for process design and tech transfer. In this study, four different freezing steps (shelf-ramped freezing with and without holding step, precooled shelves and an ice fog method for controlled nucleation) are used and their impact on primary drying experiments and simulations is shown. Only the ice fog method is able to control the nucleation temperature leading to low dry layer resistances with low deviations. During the primary drying simulations, the control of the nucleation temperature drastically increases the precision and accuracy of the product temperature prediction. For optimal primary drying design and model predictive control, the nucleation temperature is strongly recommended to be controlled inside a Process Analytical Technology (PAT) concept to achieve reliable and reproducible process conditions.
Record ID
Keywords
advanced process control (APC), controlled nucleation, lyophilization, Process Analytical Technology (PAT), process modelling, Quality by Design (QbD)
Subject
Suggested Citation
Juckers A, Knerr P, Harms F, Strube J. Effect of the Freezing Step on Primary Drying Experiments and Simulation of Lyophilization Processes. (2023). LAPSE:2023.35965
Author Affiliations
Juckers A: Institute for Separation and Process Technology, Clausthal University of Technology, 38678 Clausthal-Zellerfeld, Germany; Martin Christ Gefriertrocknungsanlagen GmbH, 37520 Osterode am Harz, Germany [ORCID]
Knerr P: Martin Christ Gefriertrocknungsanlagen GmbH, 37520 Osterode am Harz, Germany
Harms F: Martin Christ Gefriertrocknungsanlagen GmbH, 37520 Osterode am Harz, Germany
Strube J: Institute for Separation and Process Technology, Clausthal University of Technology, 38678 Clausthal-Zellerfeld, Germany
Knerr P: Martin Christ Gefriertrocknungsanlagen GmbH, 37520 Osterode am Harz, Germany
Harms F: Martin Christ Gefriertrocknungsanlagen GmbH, 37520 Osterode am Harz, Germany
Strube J: Institute for Separation and Process Technology, Clausthal University of Technology, 38678 Clausthal-Zellerfeld, Germany
Journal Name
Processes
Volume
11
Issue
5
First Page
1404
Year
2023
Publication Date
2023-05-05
Published Version
ISSN
2227-9717
Version Comments
Original Submission
Other Meta
PII: pr11051404, Publication Type: Journal Article
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Published Article
LAPSE:2023.35965
This Record
External Link
doi:10.3390/pr11051404
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Version History
[v1] (Original Submission)
Jun 7, 2023
Verified by curator on
Jun 7, 2023
This Version Number
v1
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https://psecommunity.org/LAPSE:2023.35965
Original Submitter
Calvin Tsay
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