Constant size, variable density aerosol particles by ultrasonic spray freeze drying

Suzanne M. D'Addio, John Gar Yan Chan, Philip Chi Lip Kwok, Robert K. Prud'Homme, Hak Kim Chan

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


This work provides a new understanding of critical process parameters involved in the production of inhalation aerosol particles by ultrasonic spray freeze drying to enable precise control over particle size and aerodynamic properties. A series of highly porous mannitol, lysozyme, and bovine serum albumin (BSA) particles were produced, varying only the solute concentration in the liquid feed, c s, from 1 to 5 wt%. The particle sizes of mannitol, BSA, and lysozyme powders were independent of solute concentration, and depend only on the drop size produced by atomization. Both mannitol and lysozyme formulations showed a linear relationship between the computed Fine Particle Fraction (FPF) and the square root of c s, which is proportional to the particle density, ρ, given a constant particle size d g. The FPF decreased with increasing c s from 57.0% to 16.6% for mannitol and 44.5% to 17.2% for lysozyme. Due to cohesion, the BSA powder FPF measured by cascade impaction was less than 10% and independent of c s. Ultrasonic spray freeze drying enables separate control over particle size, d g, and aerodynamic size, d a which has allowed us to make the first experimental demonstration of the widely accepted rule d a = d g(ρ/ρ o) 1/2 with particles of constant d g, but variable density, ρ (ρ o is unit density).

Original languageEnglish (US)
Pages (from-to)185-191
Number of pages7
JournalInternational Journal of Pharmaceutics
Issue number2
StatePublished - May 10 2012

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


  • Fine Particle Fraction
  • Inhalation aerosol
  • Porous particles
  • Spray freeze
  • Ultrasonic atomization


Dive into the research topics of 'Constant size, variable density aerosol particles by ultrasonic spray freeze drying'. Together they form a unique fingerprint.

Cite this