A comparative study of dry and wet top-down milling approaches for the preparation of microparticle suspensions

Fidel Méndez Cañellas, Noor Al-Rifai, Luis Padrela, Lidia Tajber, Tatsiana Khamiakova, Martin Otava, Robert Geertman

Research output: Contribution to journalArticlepeer-review

Abstract

Top-down milling methods are widely used in the pharmaceutical industry for the micronisation of active pharmaceutical ingredients (APIs). In this work, jet milling (dry milling) and microfluidisation (wet milling) were compared for the comminution of indomethacin and naproxen. A design of experiments (DoE) approach was used to setup the experimental work and determine the parameters that affect the average particle size of the API particles. The same API, excipient combinations, concentration and particle size were targeted to constitute the suspensions with both techniques, and the resultant particle size stability, solid state, and morphology were studied. Both techniques were successful in producing suspensions with a particle size of 1–10 μm and the most stable API solid form. The key parameters to mill particles to the target particle size, and a protocol to produce crystalline particle suspensions were established in this work highlighting the differences between methods.

Original languageEnglish
Article number118829
JournalPowder Technology
Volume428
DOIs
Publication statusPublished - 1 Oct 2023

Keywords

  • Active pharmaceutical ingredients
  • Design of Experiments
  • Jet milling
  • Microfluidisation
  • Microparticle suspensions
  • Stability

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