Heterogeneous particle deaggregation and its implication for therapeutic aerosol performance

Zhen Xu, Heidi M. Mansour, Tako Mulder, Richard McLean, John Langridge, Anthony J. Hickey

Research output: Contribution to journalReview articlepeer-review

21 Scopus citations

Abstract

Aerosolization performance of dry powder blends of drugs for the treatment of asthma or chronic obstructive pulmonary diseases have been reported in three previous articles. In vitro aerosolization was performed at defined shear stresses (0.624-13.143 N/m2). Formulations were characterized aerodynamically and powder aerosol deaggregation equations (PADE) and corresponding linear regression analyses for pharmaceutical aerosolization were applied. Particle deaggregation is the result of overcoming fundamental forces acting at the particle interface. A new method, PADE, describing dry powder formulation performance in a shear stress range has been developed which may allow a fundamental understanding of interparticulate and surface forces. The application of PADE predicts performance efficiency and reproducibility and supports rational design of dry powder formulations. The analogy of aerosol performance with surface molecular adsorption has important implications. Expressions describing surface adsorption were intended to allow elucidation of mechanisms involving surface heterogeneity, lateral interaction, and multilayer adsorption of a variety of materials. By using a similar expression for drug aerosolization performance, it is conceivable that an analogous mechanistic approach to the evaluation of particulate systems would be possible.

Original languageEnglish (US)
Pages (from-to)3442-3461
Number of pages20
JournalJournal of pharmaceutical sciences
Volume99
Issue number8
DOIs
StatePublished - Aug 2010
Externally publishedYes

Keywords

  • Aerosolization performance
  • Dry powder inhaler
  • Fine particle fraction
  • Interparticulate and surface forces
  • Powder aerosol deaggregation equation
  • Shear stress
  • Standardized entrainment tubes
  • Surface heterogeneity

ASJC Scopus subject areas

  • Pharmaceutical Science

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