Design of a Small-Scale Multi-Inlet Vortex Mixer for Scalable Nanoparticle Production and Application to the Encapsulation of Biologics by Inverse Flash NanoPrecipitation

Chester E. Markwalter, Robert K. Prud'homme

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Flash NanoPrecipitation is a scalable approach to generate polymeric nanoparticles using rapid micromixing in specially designed geometries such as a confined impinging jets mixer or a Multi-Inlet Vortex Mixer (MIVM). A major limitation of formulation screening using the MIVM is that a single run requires tens of milligrams of the therapeutic. To overcome this, we have developed a scaled-down version of the MIVM, requiring as little as 0.2 mg of therapeutic, for formulation screening. The redesigned mixer can then be attached to pumps for scale-up of the identified formulation. It was shown that Reynolds number allowed accurate scaling between the 2 MIVM designs. The utility of the small-scale MIVM for formulation development was demonstrated through the encapsulation of a number of hydrophilic macromolecules using inverse Flash NanoPrecipitation with target loadings as high as 50% by mass.

Original languageEnglish (US)
Pages (from-to)2465-2471
Number of pages7
JournalJournal of Pharmaceutical Sciences
Volume107
Issue number9
DOIs
StatePublished - Sep 2018

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • formulation
  • mixing
  • nanoparticles
  • particle size
  • peptide delivery
  • polymeric drug carrier
  • protein delivery

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