Abstract
The utilization of ferrets as a non-clinical model for disease is rapidly increasing within drug development. Many of these models include respiratory diseases that involve targeted drug delivery via nose-only inhalation. While the deposition patterns within other non-clinical models (mice, rats, canines, and non-human primates) have been well studied, the local and regional deposition of aerosols in ferrets has not been well characterized. Therefore, inhalation aerosols were developed, radiolabeled and the radiolabeling methods validated to support SPECT-CT imaging and quantification of regional deposition within ferrets. The studies were conducted with one liquid formulation and one dry powder formulation (two concentrations of dry powder). Additionally, both aerosols were polydisperse and therefore reflect the majority of pharmaceutical aerosols. Overall, the studies showed lung deposition fractions between 5 and 10% with median aerodynamic particle sizes of 2.5 and 2.8 μm. The lung deposition fraction of the liquid aerosol was ~ 9%, nearly double observed in rats with a similarly sized aerosol. Analysis of respiratory tract (oropharynx, laryngopharynx, trachea, bifurcation area, and lung) deposition indicates increased deposition of the liquid aerosol compared to the dry powder aerosol, however, when this analysis was refined to the pulmonary region (trachea, bifurcation, and lung) the deposition was similar between formulations. These data provide the first description of the regional deposition of inhalation aerosols in ferrets with standard nose-only inhalation procedures. These data can be used for calculations of both total and regional doses within ferret inhalation drug delivery.
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The authors would like to acknowledge the University of New Mexico Center for Isotopes in Medicine, specifically Tamara Anderson and Jeff Norenberg, for assistance with image acquisition and analysis.
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David L. Hava and Wesley H. DeHaan were employees of Pulmatrix and held an interest in commercializing products based on aspects of this work.
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Kuehl, P.J., Chand, R., McDonald, J.D. et al. Pulmonary and Regional Deposition of Nebulized and Dry Powder Aerosols in Ferrets. AAPS PharmSciTech 20, 242 (2019). https://doi.org/10.1208/s12249-019-1382-3
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DOI: https://doi.org/10.1208/s12249-019-1382-3