Impact of polymers on the aggregation of wet-milled itraconazole particles and their dissolution from spray-dried nanocomposites

Ecevit Bilgili, Mahbubur Rahman, Danny Palacios, Faustin Arevalo

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


We explore the impact of various polymers and their molecular weight on the stabilization of wet-milled suspensions of itraconazole (ITZ), a poorly soluble drug, and its dissolution from spray-dried suspensions. To this end, ITZ suspensions with SSL, SL, and L grades of hydroxypropyl cellulose (HPC) having molecular weights (MWs) of 40, 100, and 140 kg/mol, respectively, hydroxypropyl methyl cellulose (HPMC E3 with 10 kg/mol), polyvinylpyrrolidone (PVP K30 with 50 kg/mol), sodium dodecyl sulfate (SDS, surfactant), and HPC SL–SDS were wet media milled and spray-dried. Laser diffraction results show that 2.5% HPC SL–0.2% SDS led to the finest ITZ nanosuspension, whereas without SDS, only 4.5% HPC with SL/L grades ensured minimal aggregation. Rheological characterization reveals that aggregated suspensions exhibited pronounced pseudoplasticity, whereas stable suspensions exhibited near Newtonian behavior. Spray-drying yielded nanocomposites with 60–78% mean ITZ loading and acceptable content uniformity. Severe aggregation occurred during milling/drying when 4.5% polymers with MW ≤ 50 kg/mol were used; their nanocomposites exhibited incomplete redispersion due to slow matrix erosion and released ITZ slowly during dissolution test. Overall, high drug-loaded, surfactant-free ITZ nanocomposites that exhibited immediate release (>80% dissolved in 20 min) were prepared via spray-drying of wet-milled ITZ with 4.5% HPC SL/L.

Original languageEnglish (US)
Pages (from-to)2941-2956
Number of pages16
JournalAdvanced Powder Technology
Issue number12
StatePublished - Dec 2018

All Science Journal Classification (ASJC) codes

  • General Chemical Engineering
  • Mechanics of Materials


  • Dissolution enhancement
  • Drug nanoparticles
  • Polymers
  • Spray drying
  • Wet media milling


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