DELIVERY OF GLUCOCORTICOIDS BY JET NEBULIZATION - AEROSOL CHARACTERISTICS AND OUTPUT

Background: Since inflammation has been identified as a critical facto r in the pathogenesis of asthma, use of inhaled glucocorticoids has in creased. Because young children are often unable to coordinate properl y the use of metered-dose inhalers and no glucocorticoids preparations for nebulization have been approved in the United States, parenteral and intranasal glucocorticoids preparations are occasionally administe red by nebulization. Methods: We examined whether a parenteral prepara tion (triamcinolone acetonide [TAA]; Kenalog) could be delivered by ne bulization. TAA, 1000 mu g (0.1 ml), was placed in the nebulizer bowl (MB5 [MeFar, Brescia, Italy] or Pari-Jet [Dura Pharmaceuticals, San Di ego, Calif.]), then diluted with 2.9 ml normal saline solution for a t otal volume fill of 3 ml. Using a laser particle analyzer, high-perfor mance liquid chromatography, and cascade impactor, we examined the per centage of aerosol volume produced with particles in the respirable ra nge of 1 to 5 mu m in diameter actual TAA output (in micrograms) and c oncentration of TAA contained in the particles within the respirable r ange. Results: Laser particle analysis indicated that 34% +/- 3% (mean +/- SEM) (MB5) and 47 +/- 3% (Pari-Jet) of the total aerosol volume p roduced were within the respirable-range of 1 to 5 mu m in diameter, a nd this remained consistent throughout nebulization. The nebulizer was stopped serially for determination of TAA output with high-performanc e liquid chromatography. TAA output (1000 mu g less the amount in micr ograms remaining after nebulization) was essentially complete after 2 minutes with the Pari-Jet and within 4 minutes with the MB5 and totale d 352 +/- 19 mu g and 367 +/- 9 mu g, respectively. Finally, cascade i mpactor studies confirmed that 33.4% of the TAA aerosol generated by t he MB5 nebulizer was contained in particles in the respirable range. C onclusion: Approximately 35% (Pari-Jet) and 37% (MB5) of the initial 1 000 mu g of TAA was delivered with the two nebulizers tested. The part icles generated within the respirable range were limited to 34% (MB5) and 47% (Pari-Jet) of the amount delivered. TAA was equally distribute d in the particles generated. The theoretic amount delivered in the re spirable range was approximately 12.5% for the MB5 nebulizer on the ba sis of the cascade impactor and 16.5% for the Pari-Jet (assuming TAA d istribution equivalence) of the TAA placed in each of the nebulizers. Additional clinical studies are needed to define efficacy and safely i n view of the excipients used in preparing the parenteral preparation.