Quiescent and Agitated Redispersion as a Tool for Evaluating Dispersant Effectiveness in Dissolution Enhancement of Drug-Laden Nanocomposites

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Abstract

Nanocomposite microparticles (NCMPs) have been used in various solid dosage forms with the goal of enhancing the dissolution rate and bioavailability of poorly water-soluble drugs. Nanoparticle recovery from NCMPs, i.e., redispersion, is the preliminary step in drug dissolution. This study aims at exploring aqueous redispersion of NCMPs with various dispersants under quiescent vs. agitated conditions as potential dispersant screening tool in the development of fast-dissolving NCMP formulations. NCMPs were prepared by coating wet-milled suspensions of a poorly water-soluble drug, griseofulvin (GF), formulated with the dispersants hydroxypropyl cellulose (HPC), sodium dodecyl sulfate (SDS), as-received/wet co-milled croscarmellose sodium (CCS), and mannitol, onto Pharmatose® carrier particles in a fluidized bed dryer. The NCMPs were added to quiescent water kept in a cuvette, and the redispersion was visualized and investigated by turbidimetry and dynamic light scattering. The morphological evolution of a single NCMP exposed to a drop of water was studied via optical microscopy, which provided further insight into the self-redispersibility. As a comparison, the NCMPs were also redispersed in water agitated by a paddle stirrer followed by centrifugation and drug assay of the resultant supernatant, which yielded the percentage of GF recovered as nanoparticles. Both quiescent and agitated redispersion methods yielded similar rank-ordering of the dispersants: NCMPs with either HPC/SDS or HPC/CCS exhibited effective nanoparticle recovery and fast dissolution, whereas those with HPC or HPC/mannitol led to poor redispersibility and slow dissolution. This study demonstrates that both quiescent and agitated redispersion tests could be used for screening/optimizing dispersants for fast-dissolving drug NCMP formulations.

Original languageEnglish (US)
Pages (from-to)436-447
Number of pages12
JournalAAPS PharmSciTech
Volume19
Issue number1
DOIs
StatePublished - Jan 1 2018

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • bioavailability enhancement
  • drug nanoparticles
  • nanocomposite microparticles
  • nanoparticle recovery
  • redispersibility

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