Condensational growth of combination drug-excipient submicrometer particles for targeted high efficiency pulmonary delivery: comparison of CFD predictions with experimental results

Pharm Res. 2012 Mar;29(3):707-21. doi: 10.1007/s11095-011-0596-1. Epub 2011 Sep 27.


Purpose: The objective of this study was to investigate the hygroscopic growth of combination drug and excipient submicrometer aerosols for respiratory drug delivery using in vitro experiments and a newly developed computational fluid dynamics (CFD) model.

Methods: Submicrometer combination drug and excipient particles were generated experimentally using both the capillary aerosol generator and the Respimat inhaler. Aerosol hygroscopic growth was evaluated in vitro and with CFD in a coiled tube geometry designed to provide residence times and thermodynamic conditions consistent with the airways.

Results: The in vitro results and CFD predictions both indicated that the initially submicrometer particles increased in mean size to a range of 1.6-2.5 μm for the 50:50 combination of a non-hygroscopic drug (budesonide) and different hygroscopic excipients. CFD results matched the in vitro predictions to within 10% and highlighted gradual and steady size increase of the droplets, which will be effective for minimizing extrathoracic deposition and producing deposition deep within the respiratory tract.

Conclusions: Enhanced excipient growth (EEG) appears to provide an effective technique to increase pharmaceutical aerosol size, and the developed CFD model will provide a powerful design tool for optimizing this technique to produce high efficiency pulmonary delivery.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Inhalation
  • Aerosols / chemistry*
  • Bronchodilator Agents / administration & dosage*
  • Budesonide / administration & dosage*
  • Computer Simulation
  • Excipients / chemistry*
  • Humidity
  • Hydrodynamics
  • Lung / metabolism
  • Models, Chemical
  • Nebulizers and Vaporizers
  • Particle Size


  • Aerosols
  • Bronchodilator Agents
  • Excipients
  • Budesonide