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Process optimization and particle engineering of micronized drug powders via milling

Abstract

Process control and optimization is a critical aspect of process analytical technology (PAT), quality by design (QbD), and the implementation of continuous manufacturing procedures. While process control and optimization techniques have been utilized in other manufacturing industries for decades, the pharmaceutical industry has only recently begun to adopt these procedures. Micronization, particularly milling, is a generally low-yield, high-energy consumption process that is well suited for a process optimization mindset. This review discusses optimization of the pharmaceutical milling process through design space development, theoretical and empirical modeling, and monitoring of critical quality attributes.

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Correspondence to H. D. C. Smyth.

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The author (HDCS) of this paper consults for and has equity ownership in Respira Therapeutics and Nob Hill Therapeutics on inhaled product development. The terms of this arrangement have been reviewed and approved by the University of Texas at Austin in accordance with its policy on objectivity in research.

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Brunaugh, A., Smyth, H.D.C. Process optimization and particle engineering of micronized drug powders via milling. Drug Deliv. and Transl. Res. 8, 1740–1750 (2018). https://doi.org/10.1007/s13346-017-0444-x

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Keywords

  • Jet milling
  • Media milling
  • Ball milling
  • Process optimization
  • Design of experiments
  • Mathematical modeling
  • Quality by design
  • Process analytical technology