Ultrasonic nebulization system for respiratory drug delivery.
An ultrasonic spray system was tested for the production of aerosols for ultimate use in the respiratory delivery of drug to animals. A Sono-Tek ultrasonic spray system was mounted on top of a baffle to entrain aerosol particles within the carrier gas. Solvent was removed from the aerosol cloud by passing the droplets through drying columns composed of either charcoal or silica. The efficiency of removing ethanol and water were determined by measuring the outflow concentrations. Sodium fluorescein and sodium cromolyn dissolved in water were tested, and the effect of the liquid flow rate and drug concentration entering the atomizer on the output, and particle size distribution, were determined by the filter capture method, and by cascade impactor, respectively. Similar studies were conducted with budesonide and indomethacin dissolved in ethanol. The theoretical count median size distribution was calculated and compared with the experimental values calculated from the observed mass median aerodynamic diameter. The output rate expressed as the mass of aerosol collected in unit time increased nearly proportionately with the liquid flow rate (0.18-0.7 ml/min) and with the concentration of drug (0.19-12 mg/ml) entering the nebulizer. The mean particle size increased with solute concentration, but not by liquid flow rate. The calculated count median diameters were dependent on the type of solvent, but were independent of solute. At the high dose of cromolyn, there was very good agreement between the theoretical and observed. At lower doses, the observed size was larger than predicted, which was also true for the ethanol soluble solutes. The system has the potential of providing a wide range of dose levels for testing of drug delivery to animals including high doses with a controlled and relatively narrow particle size distribution.
Department of Pharmaceutics, University of Minnesota, 308 Harvard St. SE, Minneapolis, MN 55455, USA. wiedm001@tc.umn.edu
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Wiedmann
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Ravichandran
D000280:Administration, Inhalation; D000336:Aerosols; D001993:Bronchodilator Agents / Q000008:administration & dosage; D019819:Budesonide / Q000008:administration & dosage; D004205:Cromolyn Sodium / Q000737:chemistry; D004867:Equipment Design; D000431:Ethanol; D019793:Fluorescein / Q000737:chemistry; D007213:Indomethacin / Q000008:administration & dosage; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D012140:Respiratory Tract Diseases / Q000188:drug therapy; D012997:Solvents; D014465:Ultrasonics
D000336:Aerosols; D001993:Bronchodilator Agents; D012997:Solvents; D000431:Ethanol; D019819:Budesonide; D004205:Cromolyn Sodium; D019793:Fluorescein; D007213:Indomethacin