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.

Thoracoscopic Findings and Pharmacokinetics of Inhaled Fluorescein in a Pig Model

“…We found that nebulized fluorescein is rapidly absorbed in the bloodstream reaching a peak concentration approximately 20 min after initiating its administration, which is comparable to data from previous pharmacokinetic studies in experimental animals [9]. Fluorescein accumulation in visceral pleura was promptly visible after its administration, and its concentration followed a pattern similar to that in the blood, as assessed by fluorometric analysis (fig.…”

“…Aerosol administration of solid disodium fluorescein has been used in dogs to study the pulmonary and systemic deposition of drug-containing aerosols [5,6,7,8,9]. These studies showed that even a lipophobic compound such as fluorescein is absorbed rapidly via the lung when administered as an inhalation aerosol.…”

Particle Engineering for Pulmonary Drug Delivery

“…Preliminary studies suggested that the coated particles had longer retention time (significantly longer half-life) and slower release rate than the uncoated drug. Another method reported for coating from the vapor phase is condensation coating (248). Aqueous disodium fluorescein and pentamidine aerosols were dried, concentrated, and condensation Preparation of drug micro-and nanoparticles, also solid or porous composite particles for controlled release coated with paraffin wax.…”

Untitled

“…For effective deposition in the lower airways and deep lung, where drugs are most efficiently absorbed, the particle aerodynamic diameter (Dae) needs to be in the 1-5 μm range [4][5][6][7][8][9][10][11][12][13][14][15][16][17] .…”