Drug Development and Industrial Pharmacy 2008-09-01

Nicotine aerosol generation from thermally reversible zinc halide complexes using the Staccato system.

Kathleen Simis, Mingzu Lei, Amy Tsai Lu, Krishnamohan C V Sharma, Ron L Hale, Ryan Timmons, Jim Cassella

Index: Drug Dev. Ind. Pharm. 34(9) , 936-42, (2008)

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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 microg, particle fraction approximately 57%, and mean particle size approximately 0.8 microm. These results were supported by thermogravimetric analysis and differential scanning calorimetry.