Passivation of high-surface-energy sites of milled ibuprofen crystals via dry coating for reduced cohesion and improved flowability

Xi Han, Laila Jallo, Daniel To, Chinmay Ghoroi, Rajesh Davé

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Ibuprofen micronization with dry coating is investigated to examine its influence on passivation/stabilization of high-surface-energy sites and reduced cohesion. A fluid energy mill was used to micronize ibuprofen particles down to 5-28 μm with or without simultaneous nanosilica coating. Powder flow property and dispersibility were characterized using FT4 powder tester and Rodos/Helos laser diffraction particle sizer. Surface energy was characterized using a next generation inverse gas chromatography instrument. Uncoated micronized ibuprofen showed an increased Lifshitz-van der Waals (LW) dispersion component of surface energy with increasing milling intensity. In contrast, dry-coated milled powders showed a significant reduction in the LW component, whereas physical mixture of uncoated micronized ibuprofen and silica exhibited no reduction in surface energy, indicating that dry coating is necessary for the passivation of high-energy sites of ibuprofen created during micronization. Surface energy of pure micronized ibuprofen was highly heterogeneous, whereas dry-coated ibuprofen had greatly reduced heterogeneity. Micronization with dry coating also improved flowability and bulk density as compared with pure active pharmaceutical ingredient micronization without coating, or just blending with silica. Overall, dry coating leads to decreased cohesion and improved flowability because of reduced LW dispersive component of surface energy and creating nanoscale surface roughness.

Original languageEnglish (US)
Pages (from-to)2282-2296
Number of pages15
JournalJournal of Pharmaceutical Sciences
Issue number7
StatePublished - Jul 2013

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


  • Dry particle coating
  • Formulation
  • Inverse gas chromatography
  • Milling
  • Powder technology
  • Solid state
  • Surface chemistry
  • Surface energy heterogeneity


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