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

Abstract

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.

Keywords:

• nicotine
• zinc halide
• Staccato
• condensation aerosol
• thermally reversible

ACKNOWLEDGMENTS

We gratefully acknowledge the assistance of Peter Lloyd and Felicia Tsai-Fu. This work was partially funded by NIH SBIR grant R43 HL073537-01.