A combined microhydrodynamics-polymer adsorption analysis for elucidation of the roles of stabilizers in wet stirred media milling

Ecevit Bilgili, Afolawemi Afolabi

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Although polymers and surfactants are commonly used as stabilizers to impart physical stability to the suspensions produced by wet stirred media milling of poorly water-soluble drugs, scant information is available in pharmaceutical literature regarding their impact on the breakage kinetics. We present a combined microhydrodynamics-polymer adsorption analysis to elucidate the roles of stabilizers with a focus on the kinetics. Griseofulvin (GF), a model poorly water-soluble drug, was milled at various concentrations of hydroxypropyl cellulose (HPC) in the presence-absence of sodium dodecyl sulfate (SDS). Particle sizing, scanning electron microscopy, thermal analysis, and rheometry were used to determine the breakage kinetics, adsorption isotherm, and apparent viscosity, which were then used to analyze the aggregation state of the milled suspensions and the microhydrodynamics. In the absence of SDS, an increase in HPC concentration slowed the particle aggregation leading to faster apparent breakage. On the other hand, due to a synergistic stabilizing action of HPC with SDS, lower HPC concentration was needed to stabilize the suspensions, and an optimum HPC concentration for the fastest apparent breakage was identified. The microhydrodynamic analysis quantified, for the first time, the viscous dampening effect of polymers, while only the combined analysis could explain the observed optimum.

Original languageEnglish (US)
Pages (from-to)193-206
Number of pages14
JournalInternational Journal of Pharmaceutics
Volume439
Issue number1-2
DOIs
StatePublished - Dec 15 2012

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • Adsorption
  • Breakage kinetics
  • Drug nanoparticles
  • Microhydrodynamics
  • Rheology
  • Wet stirred media milling

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