Ultra-fine dispersible powders coated with L-Leucine via two-step co-milling

Zhonghui Huang, Kuriakose T. Kunnath, Xi Han, Xiaoliang Deng, Liang Chen, Rajesh N. Davé

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Dispersion of ultrafine powders is difficult due to their high cohesion and consequent agglomeration. Dry coating with additives such as nano-silica, magnesium stearate (MgSt), or Leucine (Leu), an amino acid, may help mitigate this problem. Unfortunately, when the powders to be coated are very fine, the additives such as MgSt or Leu need to be of even finer size, requiring a separate milling process. Here, a two-step co-milling process is investigated to produce well dispersible inhalable size range (<5 µm) particles. The main advantage is that the powder to be coated and additives have starting size of several hundred microns and do not require separate pre-milling. In the first step, Potassium Chloride (KCl), used as a surrogate API, and Leu are pre-milled in a ball mill to achieve KCl coated with Leu of ∼10 µm. In the second step, simultaneous co-milling via jet-milling of pre-coated KCl down to inhalable size KCl, coated with Leu is done. The dispersibility of coated KCl was assessed through laser diffraction of dry powder at low dispersion pressure (Sympatec Rodos-Helos), corroborated via scanning electron microscopy (SEM), and FT4 powder tester measuring flow function coefficient (FFC), conditioned bulk density, and aerated energy. This assessment revealed that about 2 wt% Leu was adequate to provide best overall dispersibility. The dispersibility of milled KCl after coating with Leu was found to be better compared with uncoated and MgSt or nano-silica coated KCl. Overall, this two-step co-milling of KCl with 2 wt% Leu yielded well-dispersible, <5 µm particles from starting particles of two orders of magnitude larger sizes.

Original languageEnglish (US)
Pages (from-to)2957-2965
Number of pages9
JournalAdvanced Powder Technology
Issue number12
StatePublished - Dec 2018

All Science Journal Classification (ASJC) codes

  • General Chemical Engineering
  • Mechanics of Materials


  • Amino acid
  • Co-milling
  • Dry coating
  • Fluid energy mill
  • Powder dispersion
  • Ultra-fine particles


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