The effect of film thickness on thermal aerosol generation.
OBJECTIVE
Rapid heating of thin films of pharmaceutical compounds can vaporize the molecules, which leads to formation of aerosol particles of optimal size for pulmonary drug delivery. The aim of this work was to assess the effect of coated film thickness on the purity of a thermally generated (condensation) drug aerosol.


METHODS
Pharmaceuticals in their free base form were spray-coated onto stainless steel foils and subsequently heated and vaporized in airflow via a rapid resistive heating of the foil. Aerosol particles were collected on filters, extracted, and analyzed using reverse phase HPLC to assess the amount of degradation induced during the vaporization process.


RESULTS
Condensation aerosols of five pharmaceuticals were formed from a wide range of film coating thicknesses. All five showed a roughly linear trend of increasing aerosol purity with decreasing film thickness, although with quite different slopes. These findings are consistent with a model based on general vaporization and degradation kinetics. Small non-uniformities in the film do not significantly alter aerosol purity.


CONCLUSIONS
Rapid vaporization of pharmaceuticals coated as thin films on substrates is an efficient way of generating drug aerosols. By controlling the film thickness, the amount of aerosol decomposition can be minimized to produce high purity aerosols.
Myers
Dan J
DJ
Alexza Pharmaceuticals, Inc., 1020 East Meadow Circle, Palo Alto, California 94303, USA. dmyers@alexza.com
Timmons
Ryan D
RD
Lu
Amy T
AT
Hale
Ron L
RL
Solas
Dennis W
DW
Soni
Pravin
P
Rabinowitz
Josh D
JD
D000336:Aerosols; D000465:Algorithms; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients; D007202:Indicators and Reagents; D016014:Linear Models; D010316:Particle Size; D013696:Temperature
D000336:Aerosols; D005079:Excipients; D007202:Indicators and Reagents