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A primary drying model-based comparison of conventional batch freeze-drying to continuous spin-freeze-drying for unit doses

Laurens Leys (UGent) , Brecht Vanbillemont (UGent) , Pieter-Jan Van Bockstal (UGent) , Joris Lammens (UGent) , Gust Nuytten (UGent) , Jos Corver (UGent) , Chris Vervaet (UGent) and Thomas De Beer (UGent)
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Abstract
An innovative continuous spin-freeze-drying technology for unit doses was recently developed. For this technology, a mechanistic primary drying model was developed allowing the calculation of the optimal dynamic drying trajectory for spin-frozen formulations. In this work, a model-based and experimentally verified comparison was made between conventional batch freeze-drying and spin-freeze-drying by analyzing the outputs (i.e., primary drying endpoint, optimal shelf temperature/power heater and product temperature profile) of both primary drying models. Input parameters such as dried product layer resistance (R-p) and heat input parameters (K-v, P-tot) were experimentally determined for both freeze-drying methods and compared. In addition, optimal dynamic process parameters were calculated for 3 model formulations by using both mechanistic models. Finally, model predictions were validated by measuring the product temperature and primary drying endpoint. It was observed that, when considering the same layer thickness, R-p was generally lower for continuous spin-frozen formulations compared to vials frozen in a conventional batch freeze-dryer. This observation contributes to the short primary drying times of spin-frozen formulations. In addition, as spin-freezing drastically increases the surface area of the product and lowers the dried layer thickness, drying times can be reduced even further while an excellent cake structure and appearance can still be obtained. The primary drying model for spin-frozen formulations proved to be equally accurate for the prediction of the primary drying endpoint and product temperature compared to the batch freeze-drying model.
Keywords
Freeze-drying, Continuous manufacturing, Mechanistic modelling, Mathematical modelling, Continuous freeze-drying, DESIGN SPACE, STEP, PHARMACEUTICALS, TEMPERATURE, BUILD, PART

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MLA
Leys, Laurens, et al. “A Primary Drying Model-Based Comparison of Conventional Batch Freeze-Drying to Continuous Spin-Freeze-Drying for Unit Doses.” EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, edited by Laurens Leys, vol. 157, 2020, pp. 97–107, doi:10.1016/j.ejpb.2020.09.009.
APA
Leys, L., Vanbillemont, B., Van Bockstal, P.-J., Lammens, J., Nuytten, G., Corver, J., … De Beer, T. (2020). A primary drying model-based comparison of conventional batch freeze-drying to continuous spin-freeze-drying for unit doses. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 157, 97–107. https://doi.org/10.1016/j.ejpb.2020.09.009
Chicago author-date
Leys, Laurens, Brecht Vanbillemont, Pieter-Jan Van Bockstal, Joris Lammens, Gust Nuytten, Jos Corver, Chris Vervaet, and Thomas De Beer. 2020. “A Primary Drying Model-Based Comparison of Conventional Batch Freeze-Drying to Continuous Spin-Freeze-Drying for Unit Doses.” Edited by Laurens Leys. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS 157: 97–107. https://doi.org/10.1016/j.ejpb.2020.09.009.
Chicago author-date (all authors)
Leys, Laurens, Brecht Vanbillemont, Pieter-Jan Van Bockstal, Joris Lammens, Gust Nuytten, Jos Corver, Chris Vervaet, and Thomas De Beer. 2020. “A Primary Drying Model-Based Comparison of Conventional Batch Freeze-Drying to Continuous Spin-Freeze-Drying for Unit Doses.” Ed by. Laurens Leys. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS 157: 97–107. doi:10.1016/j.ejpb.2020.09.009.
Vancouver
1.
Leys L, Vanbillemont B, Van Bockstal P-J, Lammens J, Nuytten G, Corver J, et al. A primary drying model-based comparison of conventional batch freeze-drying to continuous spin-freeze-drying for unit doses. Leys L, editor. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS. 2020;157:97–107.
IEEE
[1]
L. Leys et al., “A primary drying model-based comparison of conventional batch freeze-drying to continuous spin-freeze-drying for unit doses,” EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, vol. 157, pp. 97–107, 2020.
@article{8739975,
  abstract     = {{An innovative continuous spin-freeze-drying technology for unit doses was recently developed. For this technology, a mechanistic primary drying model was developed allowing the calculation of the optimal dynamic drying trajectory for spin-frozen formulations. In this work, a model-based and experimentally verified comparison was made between conventional batch freeze-drying and spin-freeze-drying by analyzing the outputs (i.e., primary drying endpoint, optimal shelf temperature/power heater and product temperature profile) of both primary drying models. Input parameters such as dried product layer resistance (R-p) and heat input parameters (K-v, P-tot) were experimentally determined for both freeze-drying methods and compared. In addition, optimal dynamic process parameters were calculated for 3 model formulations by using both mechanistic models. Finally, model predictions were validated by measuring the product temperature and primary drying endpoint. It was observed that, when considering the same layer thickness, R-p was generally lower for continuous spin-frozen formulations compared to vials frozen in a conventional batch freeze-dryer. This observation contributes to the short primary drying times of spin-frozen formulations. In addition, as spin-freezing drastically increases the surface area of the product and lowers the dried layer thickness, drying times can be reduced even further while an excellent cake structure and appearance can still be obtained. The primary drying model for spin-frozen formulations proved to be equally accurate for the prediction of the primary drying endpoint and product temperature compared to the batch freeze-drying model.}},
  author       = {{Leys, Laurens and Vanbillemont, Brecht and Van Bockstal, Pieter-Jan and Lammens, Joris and Nuytten, Gust and Corver, Jos and Vervaet, Chris and De Beer, Thomas}},
  editor       = {{Leys, Laurens}},
  issn         = {{0939-6411}},
  journal      = {{EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS}},
  keywords     = {{Freeze-drying,Continuous manufacturing,Mechanistic modelling,Mathematical modelling,Continuous freeze-drying,DESIGN SPACE,STEP,PHARMACEUTICALS,TEMPERATURE,BUILD,PART}},
  language     = {{eng}},
  pages        = {{97--107}},
  title        = {{A primary drying model-based comparison of conventional batch freeze-drying to continuous spin-freeze-drying for unit doses}},
  url          = {{http://dx.doi.org/10.1016/j.ejpb.2020.09.009}},
  volume       = {{157}},
  year         = {{2020}},
}

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