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Thermal Imaging as a Noncontact Inline Process Analytical Tool for Product Temperature Monitoring during Continuous Freeze-Drying of Unit Doses

(2018) Analytical Chemistry. 90(22). p.13591-13599
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Abstract
Freeze-drying is a well-established technique to improve the stability of biopharmaceuticals which are unstable in aqueous solution. To obtain an elegant dried product appearance, the temperature at the moving sublimation interface T-i should be kept below the critical product temperature T-i,T-crit during primary drying. The static temperature sensors applied in batch freeze-drying provide unreliable Ti data due to their invasive character. In addition, these sensors are incompatible with the continuous freeze-drying concept based on spinning of the vials during freezing, leading to a thin product layer spread over the entire inner vial wall. During continuous freeze-drying, the sublimation front moves from the inner side of the vial toward the glass wall, offering the unique opportunity to monitor T-i via noncontact inline thermal imaging. Via Fourier's law of thermal conduction, the temperature gradient over the vial wall and ice layer was quantified, which allowed the exact measurement of T-i during the entire primary drying step. On the basis of the obtained thermal images, the infrared (IR) energy transfer was computed via the Stefan-Boltzmann law and the dried product mass transfer resistance (R-p) profile was obtained. This procedure allows the determination of the optimal dynamic IR heater temperature profile for the continuous freeze-drying of any product. In addition, the end point of primary drying was detected via thermal imaging and confirmed by inline near-infrared (NIR) spectroscopy. Both applications show that thermal imaging is a suitable and promising process analytical tool for noninvasive temperature measurements during continuous freeze-drying, with the potential for inline process monitoring and control.
Keywords
NEAR-INFRARED SPECTROSCOPY, MASS-TRANSFER RESISTANCE, DYNAMIC DESIGN SPACE, UNCERTAINTY ANALYSIS, STEP, LYOPHILIZATION, QUALITY, OPTIMIZATION, FORMULATIONS, MODELS

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Citation

Please use this url to cite or link to this publication:

Chicago
Van Bockstal, Pieter-Jan, Jos Corver, Laurens De Meyer, Chris Vervaet, and Thomas De Beer. 2018. “Thermal Imaging as a Noncontact Inline Process Analytical Tool for Product Temperature Monitoring During Continuous Freeze-Drying of Unit Doses.” Ed. Pieter-Jan Van Bockstal. Analytical Chemistry 90 (22): 13591–13599.
APA
Van Bockstal, P.-J., Corver, J., De Meyer, L., Vervaet, C., & De Beer, T. (2018). Thermal Imaging as a Noncontact Inline Process Analytical Tool for Product Temperature Monitoring during Continuous Freeze-Drying of Unit Doses. (P.-J. Van Bockstal, Ed.)Analytical Chemistry, 90(22), 13591–13599.
Vancouver
1.
Van Bockstal P-J, Corver J, De Meyer L, Vervaet C, De Beer T. Thermal Imaging as a Noncontact Inline Process Analytical Tool for Product Temperature Monitoring during Continuous Freeze-Drying of Unit Doses. Van Bockstal P-J, editor. Analytical Chemistry. American Chemical Society (ACS); 2018;90(22):13591–9.
MLA
Van Bockstal, Pieter-Jan et al. “Thermal Imaging as a Noncontact Inline Process Analytical Tool for Product Temperature Monitoring During Continuous Freeze-Drying of Unit Doses.” Ed. Pieter-Jan Van Bockstal. Analytical Chemistry 90.22 (2018): 13591–13599. Print.
@article{8610784,
  abstract     = {Freeze-drying is a well-established technique to improve the stability of biopharmaceuticals which are unstable in aqueous solution. To obtain an elegant dried product appearance, the temperature at the moving sublimation interface T-i should be kept below the critical product temperature T-i,T-crit during primary drying. The static temperature sensors applied in batch freeze-drying provide unreliable Ti data due to their invasive character. In addition, these sensors are incompatible with the continuous freeze-drying concept based on spinning of the vials during freezing, leading to a thin product layer spread over the entire inner vial wall. During continuous freeze-drying, the sublimation front moves from the inner side of the vial toward the glass wall, offering the unique opportunity to monitor T-i via noncontact inline thermal imaging. Via Fourier's law of thermal conduction, the temperature gradient over the vial wall and ice layer was quantified, which allowed the exact measurement of T-i during the entire primary drying step. On the basis of the obtained thermal images, the infrared (IR) energy transfer was computed via the Stefan-Boltzmann law and the dried product mass transfer resistance (R-p) profile was obtained. This procedure allows the determination of the optimal dynamic IR heater temperature profile for the continuous freeze-drying of any product. In addition, the end point of primary drying was detected via thermal imaging and confirmed by inline near-infrared (NIR) spectroscopy. Both applications show that thermal imaging is a suitable and promising process analytical tool for noninvasive temperature measurements during continuous freeze-drying, with the potential for inline process monitoring and control.},
  author       = {Van Bockstal, Pieter-Jan and Corver, Jos and De Meyer, Laurens and Vervaet, Chris and De Beer, Thomas},
  editor       = {Van Bockstal, Pieter-Jan},
  issn         = {0003-2700},
  journal      = {Analytical Chemistry},
  language     = {eng},
  number       = {22},
  pages        = {13591--13599},
  publisher    = {American Chemical Society (ACS)},
  title        = {Thermal Imaging as a Noncontact Inline Process Analytical Tool for Product Temperature Monitoring during Continuous Freeze-Drying of Unit Doses},
  url          = {http://dx.doi.org/10.1021/acs.analchem.8b03788},
  volume       = {90},
  year         = {2018},
}

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