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Downscaling of the tableting process : feasibility of miniaturized forced feeders on a high-speed rotary tablet press

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Abstract
With the current transformation of the pharmaceutical industry towards continuous manufacturing, there is an inherent need to embrace this concept already during the early stages of drug formulation. Therefore, this research paper investigated the feasibility of using miniaturized forced feeders on a high-speed rotary tablet press with the intention of downscaling the tableting process. Forced feeders with a reduced volume (up to 46% compared to the conventional two-compartment forced feeder) were designed by either sealing one compartment (i.e. R&D1) or lowering of the compartment height (i.e. R&D2). These feed frame designs were thoroughly analysed in combination with two paddle types over a wide range of process-settings (i.e. tableting speed, paddle speed, direction of paddle rotation, overfill-level). A poorly flowing model powder (i.e. MCC 101) was deliberately selected as challenging formulation. Empirical modelling of feed frame R&D1 revealed a positive impact on the die-filling variability when the radial curved cuboid paddles rotated in counterclockwise direction at high paddle speed. Moreover, a strong resemblance between the R&D2 feed frame and the conventional forced feeder was observed during multivariate data analysis, indicating that this miniaturized type could be used during downscaling studies of the conventional tableting process. The potential of this forced feeder was acknowledged by the similar trends in die-filling variability with respect to varying process settings, when a design-of-experiments (DOE) was performing including feed frame type as a qualitative factor. Overall, it was concluded that both types of miniaturized forced feeders can be used on a high-speed rotary tablet press when lower material consumption rates are desired while the R&D2 feed frame bears the highest predictability regarding the diefilling uniformity in the conventional larger two-compartment forced feeder.
Keywords
Tablet manufacturing, Downscaling, R&D forced feeders, Process-engineering, Quality-by-design, Multivariate data analysis, CONTINUOUS MANUFACTURING SYMPOSIUM, COMPACTION PROPERTIES, DIE-FILL, POWDER, COMPRESSION, SIMULATOR, PRODUCTS, FLOW

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MLA
Grymonpré, Wouter, Barbora Blahova Prudilova, Valérie Vanhoorne, et al. “Downscaling of the Tableting Process : Feasibility of Miniaturized Forced Feeders on a High-speed Rotary Tablet Press.” INTERNATIONAL JOURNAL OF PHARMACEUTICS 550.1-2 (2018): 477–485. Print.
APA
Grymonpré, W., Blahova Prudilova, B., Vanhoorne, V., Van Snick, B., Detobel, F., Remon, J. P., De Beer, T., et al. (2018). Downscaling of the tableting process : feasibility of miniaturized forced feeders on a high-speed rotary tablet press. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 550(1-2), 477–485.
Chicago author-date
Grymonpré, Wouter, Barbora Blahova Prudilova, Valérie Vanhoorne, Bernd Van Snick, Frederik Detobel, Jean Paul Remon, Thomas De Beer, and Chris Vervaet. 2018. “Downscaling of the Tableting Process : Feasibility of Miniaturized Forced Feeders on a High-speed Rotary Tablet Press.” International Journal of Pharmaceutics 550 (1-2): 477–485.
Chicago author-date (all authors)
Grymonpré, Wouter, Barbora Blahova Prudilova, Valérie Vanhoorne, Bernd Van Snick, Frederik Detobel, Jean Paul Remon, Thomas De Beer, and Chris Vervaet. 2018. “Downscaling of the Tableting Process : Feasibility of Miniaturized Forced Feeders on a High-speed Rotary Tablet Press.” International Journal of Pharmaceutics 550 (1-2): 477–485.
Vancouver
1.
Grymonpré W, Blahova Prudilova B, Vanhoorne V, Van Snick B, Detobel F, Remon JP, et al. Downscaling of the tableting process : feasibility of miniaturized forced feeders on a high-speed rotary tablet press. INTERNATIONAL JOURNAL OF PHARMACEUTICS. 2018;550(1-2):477–85.
IEEE
[1]
W. Grymonpré et al., “Downscaling of the tableting process : feasibility of miniaturized forced feeders on a high-speed rotary tablet press,” INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol. 550, no. 1–2, pp. 477–485, 2018.
@article{8576924,
  abstract     = {With the current transformation of the pharmaceutical industry towards continuous manufacturing, there is an inherent need to embrace this concept already during the early stages of drug formulation. Therefore, this research paper investigated the feasibility of using miniaturized forced feeders on a high-speed rotary tablet press with the intention of downscaling the tableting process. Forced feeders with a reduced volume (up to 46% compared to the conventional two-compartment forced feeder) were designed by either sealing one compartment (i.e. R&D1) or lowering of the compartment height (i.e. R&D2). These feed frame designs were thoroughly analysed in combination with two paddle types over a wide range of process-settings (i.e. tableting speed, paddle speed, direction of paddle rotation, overfill-level). A poorly flowing model powder (i.e. MCC 101) was deliberately selected as challenging formulation. Empirical modelling of feed frame R&D1 revealed a positive impact on the die-filling variability when the radial curved cuboid paddles rotated in counterclockwise direction at high paddle speed. Moreover, a strong resemblance between the R&D2 feed frame and the conventional forced feeder was observed during multivariate data analysis, indicating that this miniaturized type could be used during downscaling studies of the conventional tableting process. The potential of this forced feeder was acknowledged by the similar trends in die-filling variability with respect to varying process settings, when a design-of-experiments (DOE) was performing including feed frame type as a qualitative factor. Overall, it was concluded that both types of miniaturized forced feeders can be used on a high-speed rotary tablet press when lower material consumption rates are desired while the R&D2 feed frame bears the highest predictability regarding the diefilling uniformity in the conventional larger two-compartment forced feeder.},
  author       = {Grymonpré, Wouter and Blahova Prudilova, Barbora and Vanhoorne, Valérie and Van Snick, Bernd and Detobel, Frederik and Remon, Jean Paul and De Beer, Thomas and Vervaet, Chris},
  issn         = {0378-5173},
  journal      = {INTERNATIONAL JOURNAL OF PHARMACEUTICS},
  keywords     = {Tablet manufacturing,Downscaling,R&D forced feeders,Process-engineering,Quality-by-design,Multivariate data analysis,CONTINUOUS MANUFACTURING SYMPOSIUM,COMPACTION PROPERTIES,DIE-FILL,POWDER,COMPRESSION,SIMULATOR,PRODUCTS,FLOW},
  language     = {eng},
  number       = {1-2},
  pages        = {477--485},
  title        = {Downscaling of the tableting process : feasibility of miniaturized forced feeders on a high-speed rotary tablet press},
  url          = {http://dx.doi.org/10.1016/j.ijpharm.2018.09.006},
  volume       = {550},
  year         = {2018},
}

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