Controlled dissolution from wax-coated aerosol particles in canine lungs.

Abstract

Treatment of pulmonary and systemic diseases may be improved and toxicity reduced by pulmonary deposition of drug-containing aerosols exhibiting delayed dissolution. Aqueous disodium fluorescein and pentamidine aerosols were dried, concentrated, and condensation coated with paraffin wax. The apparent mass median aerodynamic diameters of the coated fluorescein particles were 2.8-4.0 microns. Wax-to-fluorescein ratios were 0.38-1.05. The dissolution half times determined using a single-pass flow system were 1.5 min for uncoated fluorescein and 0.8 min for uncoated pentamidine. These increased over threefold when the aerosols were coated with paraffin wax to maxima of 5.3 and 2.6 min, respectively. Wax-coated aerosols generated from fluorescein mixed with 99mTc-labeled iron oxide colloid delivered to the canine lungs demonstrated a 3.4-fold increase in the absorption half time of disodium fluorescein compared with uncoated fluorescein (11.2 vs. 38.4 min). The absence of changes in pulmonary function on inhalation of these wax-coated aerosols, together with a high drug load and delayed release, establishes a foundation for future therapeutic applications.