GENERATION OF CONCENTRATED AEROSOLS FOR INHALATION STUDIES

A technique is described for generation of concentrated respirable aerosols and their administration to canine lungs. The functional characteristics of the system were delineated using aqueous solutions of disodium fluorescein (DF). The aerosol was generated by delivering pressurized air and disodium fluorescein solution to a Turbotac jet nebulizer. The particles were dried with a sheath of warm air and concentrated using a seven orifice virtual impactor. The input aerosol particles were concentrated up to eight times, resulting in output aerosol concentration of about 10 mg m-3 at a flow rate of 20 1 min-1. The particles had predictable mass median aerodynamic diameters between 4 and 7 mum, and geometric standard deviations between 1.7 and 2.0. To conduct inhalation studies on beagle dogs, the aerosol generation and concentration system was pressurized to 18 cm of water. In these experiments the test aerosol consisted of a mixture of disodium fluorescein with technetium-99m tagged to iron oxide colloid, controlled delivery of the aerosol to the dogs was achieved by sequencing low resistance solenoid valves using a logic control box. The animals were anesthetized and endotracheally intubated. The aerosols were carried in the ventilating air stream. The duration of exposure was 3 min. Gamma scintigraphy confirmed deposition of the aerosol in the lower lungs as demonstrated by a total lung retention between 70 and 75% after 24 h. This methodology is applicable for use with solutions and/or colloidal suspensions and can be adapted for continuous aerosol generation and delivery.