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

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Abstract

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.

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Authors and Affiliations

  1. Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ, 08854, USA

    Patricia M. Portillo, Marianthi Ierapetritou, Silvina Tomassone & Fernando J. Muzzio

  2. Process Technologies, Glaxo Smith Kline Company, 709 Swedeland Road, King of Prussia, PA, 19406, USA

    Christine Mc Dade & Donald Clancy

  3. GlaxoSmithKline R&D, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK

    Petrus P. C. Avontuur

Authors
  1. Patricia M. Portillo
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  2. Marianthi Ierapetritou
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  3. Silvina Tomassone
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  4. Christine Mc Dade
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  5. Donald Clancy
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  6. Petrus P. C. Avontuur
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  7. Fernando J. Muzzio
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Correspondence to Fernando J. Muzzio.

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Portillo, P.M., Ierapetritou, M., Tomassone, S. et al. Quality by Design Methodology for Development and Scale-up of Batch Mixing Processes. J Pharm Innov 3, 258–270 (2008). https://doi.org/10.1007/s12247-008-9048-9

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  • DOI: https://doi.org/10.1007/s12247-008-9048-9

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