Simultaneous micronization and surface modification for improvement of flow and dissolution of drug particles

Xi Han, Chinmay Ghoroi, Daniel To, Yuhua Chen, Rajesh Davé

Research output: Contribution to journalArticlepeer-review

146 Scopus citations


Simultaneous micronization and surface modification of drug particles is considered in order to mitigate disadvantages of micronization, e.g.; agglomeration, poor flowability, marginal increase in surface area and low bulk density. Particles of ibuprofen (102 μm), a model drug, pre-blended with hydrophilic nano-silica, are micronized down to 10 and 5 μm in a continuous fluid energy mill (FEM) to obtain fine surface modified particles. The solid feeding rate and the grinding pressure are shown as critical parameters for achieving the desired particle size and size distribution. The powder properties were characterized via SEM, laser scattering, powder rheometer with shear-cell, and dissolution test. Significant improvement in flow properties and dissolution rate was observed when micronization accompanied surface modification. Additionally, co-grinding with water-soluble polymer during micronization led to further increase in bulk density and more enhanced dissolution rate improvement, which is attributed to improved wettability. XRD, DSC and Raman were used to examine crystallinity, indicating minimal detectable physical transformation with FEM processed ibuprofen. The surface modified, micronized powders also showed improved dispersion, higher bulk densities (>0.4 g/ml), reduced electrostatic, and higher flowability (FFC ≥ 6) compared to just micronized powder (0.19 g/ml, FFC = 1.0), indicating they may be used in high drug loaded formulations amenable to direct compression.

Original languageEnglish (US)
Pages (from-to)185-195
Number of pages11
JournalInternational Journal of Pharmaceutics
Issue number1-2
StatePublished - Aug 30 2011

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


  • Co-grinding
  • Dissolution rate
  • Dry coating
  • Flowability
  • Fluid energy mill (FEM)
  • Micronization


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