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Impact of blend properties on die filling during tableting

Bernd Van Snick (UGent) , Wouter Grymonpré (UGent) , Jens Dhondt (UGent) , Kenny Pandelaere (UGent) , G Di Pretoro, Jean Paul Remon (UGent) , Thomas De Beer (UGent) , Chris Vervaet (UGent) and Valérie Vanhoorne (UGent)
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Abstract
Based on characterization of a wide range of fillers and APIs, thirty divergent blends were composed and subsequently compressed on a rotary tablet press, varying paddle speed and turret speed. The tablet weight variability was determined of 20 grab samples consisting of each 20 tablets. Additionally, the bulk residence time, ejection force, pre-compression displacement, main compression force, die fill fraction and feed frame fill fraction were determined during each run. Multivariate data analysis was applied to investigate the relation between the process parameters, blend characteristics, product and process responses. Blends with metoprolol tartrate as API showed high ejection forces. This behavior could be linked to the high wall friction value of metoprolol tartrate. The main responses related to the die filling could be predicted via a PLS model based on blend characteristics. Tablet weight variability was highly correlated with the variability on pre-compression displacement and main compression force. A good predictive model for tablet weight variability was obtained taking the porosity, wall friction angle, flowability, density, compressibility and permeability into account. Additionally, turret speed and paddle speed were included in the calibration of the model. The applied approach can save resources (material, time) during early drug product development.
Keywords
Continuous direct compression, Continuous manufacturing, Tableting, Die filling, Blend properties, PLS model, CONTINUOUS DIRECT COMPRESSION, POWDER FLOW PROPERTIES, FORMULATION DESIGN, WEIGHT VARIABILITY, FORCED FEEDER, SPEED, PRESS, PARACETAMOL, PRODUCTS, PLATFORM

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MLA
Van Snick, Bernd et al. “Impact of Blend Properties on Die Filling During Tableting.” INTERNATIONAL JOURNAL OF PHARMACEUTICS 549.1-2 (2018): 476–488. Print.
APA
Van Snick, Bernd, Grymonpré, W., Dhondt, J., Pandelaere, K., Di Pretoro, G., Remon, J. P., De Beer, T., et al. (2018). Impact of blend properties on die filling during tableting. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 549(1-2), 476–488.
Chicago author-date
Van Snick, Bernd, Wouter Grymonpré, Jens Dhondt, Kenny Pandelaere, G Di Pretoro, Jean Paul Remon, Thomas De Beer, Chris Vervaet, and Valérie Vanhoorne. 2018. “Impact of Blend Properties on Die Filling During Tableting.” International Journal of Pharmaceutics 549 (1-2): 476–488.
Chicago author-date (all authors)
Van Snick, Bernd, Wouter Grymonpré, Jens Dhondt, Kenny Pandelaere, G Di Pretoro, Jean Paul Remon, Thomas De Beer, Chris Vervaet, and Valérie Vanhoorne. 2018. “Impact of Blend Properties on Die Filling During Tableting.” International Journal of Pharmaceutics 549 (1-2): 476–488.
Vancouver
1.
Van Snick B, Grymonpré W, Dhondt J, Pandelaere K, Di Pretoro G, Remon JP, et al. Impact of blend properties on die filling during tableting. INTERNATIONAL JOURNAL OF PHARMACEUTICS. 2018;549(1-2):476–88.
IEEE
[1]
B. Van Snick et al., “Impact of blend properties on die filling during tableting,” INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol. 549, no. 1–2, pp. 476–488, 2018.
@article{8609698,
  abstract     = {Based on characterization of a wide range of fillers and APIs, thirty divergent blends were composed and subsequently compressed on a rotary tablet press, varying paddle speed and turret speed. The tablet weight variability was determined of 20 grab samples consisting of each 20 tablets. Additionally, the bulk residence time, ejection force, pre-compression displacement, main compression force, die fill fraction and feed frame fill fraction were determined during each run. Multivariate data analysis was applied to investigate the relation between the process parameters, blend characteristics, product and process responses. Blends with metoprolol tartrate as API showed high ejection forces. This behavior could be linked to the high wall friction value of metoprolol tartrate. The main responses related to the die filling could be predicted via a PLS model based on blend characteristics. Tablet weight variability was highly correlated with the variability on pre-compression displacement and main compression force. A good predictive model for tablet weight variability was obtained taking the porosity, wall friction angle, flowability, density, compressibility and permeability into account. Additionally, turret speed and paddle speed were included in the calibration of the model. The applied approach can save resources (material, time) during early drug product development.},
  author       = {Van Snick, Bernd and Grymonpré, Wouter and Dhondt, Jens and Pandelaere, Kenny and Di Pretoro, G and Remon, Jean Paul and De Beer, Thomas and Vervaet, Chris and Vanhoorne, Valérie},
  issn         = {0378-5173},
  journal      = {INTERNATIONAL JOURNAL OF PHARMACEUTICS},
  keywords     = {Continuous direct compression,Continuous manufacturing,Tableting,Die filling,Blend properties,PLS model,CONTINUOUS DIRECT COMPRESSION,POWDER FLOW PROPERTIES,FORMULATION DESIGN,WEIGHT VARIABILITY,FORCED FEEDER,SPEED,PRESS,PARACETAMOL,PRODUCTS,PLATFORM},
  language     = {eng},
  number       = {1-2},
  pages        = {476--488},
  title        = {Impact of blend properties on die filling during tableting},
  url          = {http://dx.doi.org/10.1016/j.ijpharm.2018.08.015},
  volume       = {549},
  year         = {2018},
}

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