Ron L. Hale

The Effect of Film Thickness on Thermal Aerosol Generation

PurposeRapid 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.Materials and MethodsPharmaceuticals 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.ResultsCondensation 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.ConclusionsRapid 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.

Nicotine Aerosol Generation from Thermally Reversible Zinc Halide Complexes Using the Staccato® System

Application of the Staccato system to liquid drugs presents unique technological challenges. Liquids, such as nicotine, do not form physically stable films on vaporization substrates. We identified two thermally reversible zinc halides (ZnCl2 and ZnBr2) that complex with nicotine in a 1:2 mol ratio (zinc halide: nicotine) that can be coated as a solid film. Feasibility studies indicated that the chloride complex liberates a higher fraction of nicotine upon heating whereas the nicotine aerosol purity for both complexes was approximately 99%. Using a multidose Staccato device previously used in a Phase I clinical trial, we demonstrated that highly pure nicotine aerosol can be reliably generated from the chloride complex with the following qualities: aerosol purity approximately 99%, single emitted dose approximately 117 μg, particle fraction approximately 57%, and mean particle size approximately 0.8 μm. These results were supported by thermogravimetric analysis and differential scanning calorimetry.