Investigation of the changes in aerosolization behavior between the jet-milled and spray-dried colistin powders through surface energy characterization

Teresa Jong, Jian Li, David A. V. Morton, Qi (Tony) Zhou, Ian Larson

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This study aimed to investigate the surface energy factors behind improved aerosolization performance of spray-dried colistin powder formulations compared with those produced by jet milling. Inhalable colistin powder formulations were produced by jet milling or spray drying (with or without l-leucine). Scanning electron micrographs showed the jet-milled particles had irregularly angular shapes, whereas the spray-dried particles were more spherical. Significantly higher fine particle fractions were measured for the spray-dried (43.8%-49.6%) versus the jet-milled formulation (28.4%) from a Rotahaler at 60 L/min; albeit the size distribution of the jet-milled powder was smaller. Surprisingly, addition of l-leucine in the spray drying feed solution gave no significant improvement in fine particle fraction. As measured by inverse gas chromatography, spray-dried formulations had significantly (p < 0.001) lower dispersive, specific, and total surface energy values and more uniform surface energy distributions than the jet-milled powder. Interestingly, no significant difference was measured in the specific and total surface energy values between the spray-dried formulation with or without l-leucine. Based on our previous findings in the self-assembling behavior of colistin in aqueous solution and the surface energy data obtained here, we propose the self-assembly of colistin molecules during spray drying contributed significantly to the reduction of surface free energy and the superior aerosolization performance.

Original languageEnglish
Pages (from-to)1156-1163
Number of pages8
JournalJournal of Pharmaceutical Sciences
Issue number3
Publication statusPublished - 1 Mar 2016


  • antibiotics
  • colistin
  • dry powder inhaler
  • inverse gas chromatography
  • jet milling
  • respiratory infection
  • self-assembly
  • spray drying
  • surface energy

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