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. Muzzio

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)258-270
Number of pages13
JournalJournal of Pharmaceutical Innovation
Volume3
Issue number4
DOIs
StatePublished - 2008

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Drug Discovery

Keywords

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

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