The droplet or particle size of an aerosol is a critical factor in defining the site of deposition of the drug in the patient’s airways (Gonda, 1990). A distribution of particle or droplet size of 1 to 6 µm was determined to be optimal for the uniform deposition of rhDNase I in the airways (Cipolla et al., 1994). Jet nebulizers have been used since they are the simplest method of producing aerosols in the desired respirable range. However, recirculation of protein solutions under high shear rates in the nebulizer bowl can present risks to the integrity of the protein molecule. rhDNase I survived recirculation and high shear rates during the nebulization process with no apparent degrada-tion in protein quality or enzymatic activity (Cipolla et al., 1994).
Approved nebulizers produce aerosol droplets in the respirable range (1–6 µm) with a mass median aerodynamic diameter (MMAD) of 4 to 6 µm. The delivery of rhDNase I with a device that produces smaller droplets leads to more peripheral deposition in the smaller airways and thereby improves efficacy (Geller et al., 1998). Results obtained in 749 CF patients with mild disease confirmed that patients randomized to the Sidestream nebulizer powered by the Mobil Aire Compressor (MMAD ¼ 2.1 µm) tended to have greater improvement in pulmonary function than patients using the Hudson T nebulizer with PulmoAide Compressor (MMAD ¼ 4. µm). These re-sults indicate that the efficacy of rhDNase I is dependent, in part, on the physical properties of the aerosol produced by the delivery system.