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Modelling the primary drying step for the determination of the optimal dynamic heating pad temperature in a continuous pharmaceutical freeze-drying process for unit doses

Laurens De Meyer (UGent) , Joris Lammens (UGent) , Séverine Mortier (UGent) , Brecht Vanbillemont (UGent) , Pieter-Jan Van Bockstal (UGent) , Jos Corver (UGent) , Ingmar Nopens (UGent) , Chris Vervaet (UGent) and Thomas De Beer (UGent)
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Abstract
In the pharmaceutical industry, traditional freeze-drying of unit doses is a batch-wise process associated with many disadvantages. To overcome these disadvantages and to guarantee a uniform product quality and high process efficiency, a continuous freeze-drying process is developed and evaluated. The main differences between the proposed continuous freeze-drying process and traditional freeze-drying can be found firstly in the freezing step during which the vials are rotated around their longitudinal axis (spin freezing), and secondly in the drying step during which the energy for sublimation and desorption is provided through the vial wall by conduction via an electrical heating pad. To obtain a more efficient drying process, the energy transfer has to be optimised without exceeding the product and process limits (e.g. cake collapse, choked flow). Therefore, a mechanistic model describing primary drying during continuous lyophilisation of unit doses based on conduction via heating pads was developed allowing the prediction of the optimal dynamic power input and temperature output of the electric heating pads. The model was verified by experimentally testing the optimal dynamic primary drying conditions calculated for a model formulation. The primary drying endpoint of the model formulation was determined via in-line NIR spectroscopy. This endpoint was then compared with the predicted model based endpoint. The mean ratio between the experimental and model based predicted drying time for six verification runs was 1.05 +/- 0.07, indicating a good accordance between the model and the experimental data.
Keywords
Continuous freeze-drying, Mathematical modelling, Conduction, NIR spectroscopy, Mechanistic modelling, Spin freezing, DESIGN SPACE

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Citation

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

Chicago
De Meyer, Laurens, Joris Lammens, Séverine Mortier, Brecht Vanbillemont, Pieter-Jan Van Bockstal, Jos Corver, Ingmar Nopens, Chris Vervaet, and Thomas De Beer. 2017. “Modelling the Primary Drying Step for the Determination of the Optimal Dynamic Heating Pad Temperature in a Continuous Pharmaceutical Freeze-drying Process for Unit Doses.” International Journal of Pharmaceutics 532 (1): 185–193.
APA
De Meyer, Laurens, Lammens, J., Mortier, S., Vanbillemont, B., Van Bockstal, P.-J., Corver, J., Nopens, I., et al. (2017). Modelling the primary drying step for the determination of the optimal dynamic heating pad temperature in a continuous pharmaceutical freeze-drying process for unit doses. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 532(1), 185–193.
Vancouver
1.
De Meyer L, Lammens J, Mortier S, Vanbillemont B, Van Bockstal P-J, Corver J, et al. Modelling the primary drying step for the determination of the optimal dynamic heating pad temperature in a continuous pharmaceutical freeze-drying process for unit doses. INTERNATIONAL JOURNAL OF PHARMACEUTICS. 2017;532(1):185–93.
MLA
De Meyer, Laurens, Joris Lammens, Séverine Mortier, et al. “Modelling the Primary Drying Step for the Determination of the Optimal Dynamic Heating Pad Temperature in a Continuous Pharmaceutical Freeze-drying Process for Unit Doses.” INTERNATIONAL JOURNAL OF PHARMACEUTICS 532.1 (2017): 185–193. Print.
@article{8542282,
  abstract     = {In the pharmaceutical industry, traditional freeze-drying of unit doses is a batch-wise process associated with many disadvantages. To overcome these disadvantages and to guarantee a uniform product quality and high process efficiency, a continuous freeze-drying process is developed and evaluated. The main differences between the proposed continuous freeze-drying process and traditional freeze-drying can be found firstly in the freezing step during which the vials are rotated around their longitudinal axis (spin freezing), and secondly in the drying step during which the energy for sublimation and desorption is provided through the vial wall by conduction via an electrical heating pad. To obtain a more efficient drying process, the energy transfer has to be optimised without exceeding the product and process limits (e.g. cake collapse, choked flow). Therefore, a mechanistic model describing primary drying during continuous lyophilisation of unit doses based on conduction via heating pads was developed allowing the prediction of the optimal dynamic power input and temperature output of the electric heating pads. The model was verified by experimentally testing the optimal dynamic primary drying conditions calculated for a model formulation. The primary drying endpoint of the model formulation was determined via in-line NIR spectroscopy. This endpoint was then compared with the predicted model based endpoint. The mean ratio between the experimental and model based predicted drying time for six verification runs was 1.05 +/- 0.07, indicating a good accordance between the model and the experimental data.},
  author       = {De Meyer, Laurens and Lammens, Joris and Mortier, S{\'e}verine and Vanbillemont, Brecht and Van Bockstal, Pieter-Jan and Corver, Jos and Nopens, Ingmar and Vervaet, Chris and De Beer, Thomas},
  issn         = {0378-5173},
  journal      = {INTERNATIONAL JOURNAL OF PHARMACEUTICS},
  keyword      = {Continuous freeze-drying,Mathematical modelling,Conduction,NIR spectroscopy,Mechanistic modelling,Spin freezing,DESIGN SPACE},
  language     = {eng},
  number       = {1},
  pages        = {185--193},
  title        = {Modelling the primary drying step for the determination of the optimal dynamic heating pad temperature in a continuous pharmaceutical freeze-drying process for unit doses},
  url          = {http://dx.doi.org/10.1016/j.ijpharm.2017.09.004},
  volume       = {532},
  year         = {2017},
}

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