Impact of matrix surface area on griseofulvin release from extrudates prepared via nanoextrusion

Meng Li, Casey Furey, Jeffrey Skros, Olivia Xu, Mahbubur Rahman, Mohammad Azad, Rajesh Dave, Ecevit Bilgili

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


We aimed to examine the impact of milling of extrudates prepared via nanoextrusion and the resulting matrix surface area of the particles on griseofulvin (GF, a model poorly soluble drug) release during in vitro dissolution. Wet-milled GF nanosuspensions containing a polymer (Sol: Soluplus®, Kol: Kolliphor® P407, or HPC: Hydroxypropyl cellulose) and sodium dodecyl sulfate were mixed with additional polymer and dried in an extruder. The extrudates with 2% and 10% GF loading were milled–sieved into three size fractions. XRPD–SEM results show that nanoextrusion produced GF nanocomposites with Kol/HPC and an amorphous solid dispersion (ASD) with Sol. For 8.9 mg GF dose (non-supersaturating condition), the dissolution rate parameter was higher for extrudates with higher external specific surface area and those with 10% drug loading. It exhibited a monotonic increase with surface area of the ASD, whereas its increase tended to saturate above ~30 × 10−3 m2 /cm3 for the nanocomposites. In general, the nanocomposites released GF faster than the ASD due to greater wettability and faster erosion imparted by Kol/HPC than by Sol. For 100 mg GF dose, the ASD outperformed the nanocomposites due to supersaturation and only 10% GF ASD with 190 × 10−3 m2 /cm3 surface area achieved immediate release (80% release within 30 min). Hence, this study suggests that ASD extrudates entail fine milling yielding > ~200 × 10−3 m2 /cm3 for rapid drug release, whereas only a coarse milling yielding ~30 × 10−3 m2 /cm3 may enable nanocomposites to release low-dose drugs rapidly.

Original languageEnglish (US)
Article number1036
Issue number7
StatePublished - Jul 2021

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


  • Amorphous solid dispersion
  • Dissolution
  • Nanocomposites
  • Nanoextrusion
  • Wet media milling
  • Wetta-bility


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