A study of the physical stability of wet media-milled fenofibrate suspensions using dynamic equilibrium curves

C. Knieke, M. A. Azad, R. N. Davé, E. Bilgili

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78 Scopus citations


Physical stability of wet media-milled fenofibrate (FNB, drug) suspensions containing stabilizers hydroxypropyl methyl cellulose (HPMC) and sodium dodecyl sulfate (SDS) is investigated. Traditionally, optimal stabilizer concentration is determined by assessing the particle size after milling and during storage in a multitude of experiments. Here, in a novel approach, similar physical stability information is generated via stepwise addition of a stabilizer at the end of milling in a single experiment and it is represented by a dynamic equilibrium curve. Such curves were generated for HPMC, SDS, and HPMC-SDS after milling and after 7-day storage. A unique optimal SDS concentration was found irrespective of the HPMC concentration (above a minimum), which was governed by agglomeration at low SDS concentration and by Ostwald ripening at high SDS concentration. Additional milling experiments with initial stabilizer addition instead of stepwise addition validated the new method, i.e. dynamic equilibrium curves via stepwise addition, which also revealed guiding principles for a stable FNB suspension. Unlike initial addition of SDS in multiple experiments, stepwise addition at the end of milling yielded the dynamic equilibrium curve in a single experiment for the 0.5-5% SDS concentration (wrt FNB), which resulted in 75% time saving and 83% drug saving.

Original languageEnglish (US)
Pages (from-to)1245-1258
Number of pages14
JournalChemical Engineering Research and Design
Issue number7
StatePublished - Jul 2013

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Chemical Engineering


  • Dynamic equilibrium
  • Fenofibrate
  • Nanoparticles
  • Stabilization
  • Wet media milling


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