Related Experiment Video
Updated: Nov 8, 2025
08:55
Formulations for Freeze-drying of Bacteria and Their Influence on Cell Survival
Published on: August 3, 2013
23.9K
Temperature Based Process Characterization of Pharmaceutical Freeze-Thaw Operations.
Dennis Weber1, Jürgen Hubbuch1
1Institute of Engineering in Life Sciences, Section IV: Biomolecular Separation Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.
Frontiers in Bioengineering and Biotechnology
|April 26, 2021
Summary
Accurate freeze-thaw characterization in biopharma requires precise freezing time detection. A new method using Fiber-Bragg-Grating sensors improves understanding of freeze concentration effects on product stability.
Area of Science:
- Biopharmaceutical Manufacturing
- Process Engineering
- Analytical Chemistry
Background:
- Freeze-thaw operations are critical for biopharmaceutical product stability during storage.
- These operations can induce stresses, like freeze concentration gradients, potentially reducing protein activity.
- Current methods for characterizing freeze-thaw processes often lack precision due to temperature probe limitations.
Purpose of the Study:
- To develop and validate a novel method for accurate freezing time detection in biopharmaceutical freeze-thaw processes.
- To investigate the impact of freezing time and boundary effects on product stability.
- To characterize a new small-scale freeze-thaw device.
Main Methods:
- Utilized Fiber-Bragg-Grating sensors for temperature measurements.
- Applied a second derivative analysis of temperature data to detect freezing points accurately.
- Employed the Plank equation and an empirically extended model for freezing time estimation.
- Analyzed 2D-resolved temperature profiles.
Main Results:
- A new method based on the second derivative of temperature measurements accurately detects freezing times.
- Freezing times ranged from 35 to 81 minutes across tested temperatures (-60 to -20°C).
- Freeze concentration profiles were significantly impacted by freezing times.
- Limitations of the Plank equation were identified and addressed with an extended model.
Conclusions:
- The developed method overcomes limitations of traditional temperature probes for freeze-thaw characterization.
- Freezing time is a critical parameter influencing freeze concentration and product stability.
- In small containers, freezing temperature may be less critical than freezing distance for freeze concentration effects.
Related Concept Videos
02:39Phase Transitions: Melting and Freezing
13.7K
Heating a crystalline solid increases the average energy of its atoms, molecules, or ions, and the solid gets hotter. At some point, the added energy becomes large enough to partially overcome the forces holding the molecules or ions of the solid in their fixed positions, and the solid begins the process of transitioning to the liquid state or melting. At this point, the temperature of the solid stops rising, despite the continual input of heat, and it remains constant until all of the solid is...
13.7K
01:03Sublimation
1.9K
Sublimation is the direct transformation of a solid to a gaseous state. For instance, at standard pressure and room temperature, solid carbon dioxide sublimes to gaseous carbon dioxide. The phase diagram depicts the conditions required for sublimation. This process occurs at the solid-gas phase boundary and is not observed above the triple point of the substance. The reverse of sublimation is called deposition, where a gaseous substance condenses directly into a solid. Sublimation and...
1.9K
01:23Physical Methods for Controlling Microbial Growth: Temperature
680
Heat is a widely used method to control microbial growth by targeting and denaturing cellular proteins, thereby killing or inactivating microbes. This method's effectiveness is quantified using parameters such as the thermal death point (TDP), thermal death time (TDT), and decimal reduction time (D value). TDP represents the lowest temperature at which all microorganisms in a liquid suspension are eliminated within 10 minutes, whereas TDT is the time necessary to achieve sterilization at a...
680
01:09In Vitro Drug Dissolution: Compendial Testing Models II
50
Various dissolution methods are utilized to assess a drug’s dissolution rate, including the flow-through cell, paddle-over-disk, cylinder, and reciprocating disk methods.The flow-through cell apparatus (USP (United States Pharmacopeia) method 4) comprises a reservoir for the dissolution medium and a pump that propels the medium through the cell containing the test sample. This method is crucial for assessing modified-release dosage forms with minimally soluble active ingredients,...
50
01:14Drug Dissolution: Requirements and Profile Comparison
87
The acceptance criteria for dissolution profile data are anchored in Q values, representing the percentage of drug dissolved within a specified period. This assessment unfolds in three stages:First Stage: The test passes if all six drug dosage units are equal to or greater than Q plus 5%; otherwise, the sample proceeds to the second stage.Second Stage: The average of twelve units must be equal to or greater than Q, with no unit falling below Q - 15% to pass; if not, it progresses to the final...
87