Journal of Pharmaceutical Innovation

, Volume 3, Issue 4, pp 258–270 | Cite as

Quality by Design Methodology for Development and Scale-up of Batch Mixing Processes

  • Patricia M. Portillo
  • Marianthi Ierapetritou
  • Silvina Tomassone
  • Christine Mc Dade
  • Donald Clancy
  • Petrus P. C. Avontuur
  • Fernando J. MuzzioEmail author
Research Article


In this study, a quality by design approach was applied to the design and scale-up of a batch mixing process. Mixtures of acetaminophen and lactose were sampled at different mixing times using a groove sampler. Samples were subsequently analyzed using NIR reflection spectroscopy. The effects of four processing parameters on the empirical mixing rate in a bin blender were examined. Blender rotation rate (two levels), powder fill level (two levels), powder cohesion (two levels), and blender size (three levels) represent the four parameters studied. Blender geometry and blender loading method were treated as constant parameters. Statistical analysis was used to assess the impact each parameter had on the mixing rate. Blender size (p = 0.02), powder cohesion (p = 0.05), and rotation rate (p = 0.07) all significantly affected the mixing rate. The least significant parameter was the vessel fill level (p = 0.18), indicating mixing performance is not strongly affected by fill level, given the range studied.


Quality by design Batch powder mixing Bin blender Statistical analysis Mixing rate 


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Copyright information

© International Society for Pharmaceutical Engineering 2008

Authors and Affiliations

  • Patricia M. Portillo
    • 1
  • Marianthi Ierapetritou
    • 1
  • Silvina Tomassone
    • 1
  • Christine Mc Dade
    • 2
  • Donald Clancy
    • 2
  • Petrus P. C. Avontuur
    • 3
  • Fernando J. Muzzio
    • 1
    Email author
  1. 1.Department of Chemical and Biochemical EngineeringRutgers UniversityPiscatawayUSA
  2. 2.Process TechnologiesGlaxo Smith Kline CompanyKing of PrussiaUSA
  3. 3.GlaxoSmithKline R&D, New Frontiers Science ParkEssexUK

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