ABSTRACT
Pharmaceutical aerosols have the potential to prevent pulmonary infectious diseases. Liposomal amphotericin B (LAMB, Ambisome, Astellas Pharma US, Deerfield, IL, USA) is approved as an intravenous infusion for empiric treatment of presumed fungal infections in neutropenic, febrile patients, as well as patients infected with Aspergillus, Cryptococcus, and other fungal pathogens. In this study, four different nebulizers were tested for their ability to deliver LAMB in aerodynamic droplet-size ranges relevant to lung deposition by an inertial sampling technique Mass median aerodynamic diameter (MMAD) and fine particle fraction percent <3.3 µm (FPF(3.3)) and <5.8 µm (FPF(5.8)) were determined by cascade impaction during a 2 min sampling period for each of three trials of all nebulizers. The MMADs for all nebulizers ranged from 1.72 ± 0.11 µm to 2.89 ± 0.12 µm; FPF(3.3) and FPF(5.8) were approximately 80% and 90%, respectively. Although all nebulizers appear acceptable for delivery of LAMB, the Pari LC Star and the Aeroeclipse II were considered the best in terms of delivery of aerosol efficiently and the proportion suitable for lung deposition. Additional research on pulmonary delivery and clinical tolerability is warranted.
Subject(s)
Amphotericin B/administration & dosage , Antifungal Agents/administration & dosage , Nebulizers and Vaporizers , Administration, Inhalation , Aerosols , Drug Delivery Systems , Equipment Design , Particle SizeABSTRACT
STUDY OBJECTIVES: To determine the optimal nebulization system for aerosolizing micafungin and to further assess the physiochemical properties of aerosolized micafungin. DESIGN: In vitro experiment. SETTING: University research center. NEBULIZERS: Pari LC Star, Hudson Updraft, Small Volume Nebulizer, and Aeroclipse II. MEASUREMENTS AND MAIN RESULTS: Using a commercially available cascade impactor, the four nebulizers were tested for their ability to deliver micafungin to the lungs. Mass median aerodynamic diameter (MMAD) and fine particle fraction (FPF) percent less than 3.3 µm (FPF(3.3)) and less than 5.8 µm (FPF(5.8)) were determined during two sampling periods for each of three trials of all nebulizers. The mean ± standard error of the mean MMAD for the nebulizers ranged from 1.93 ± 0.09 to 2.49 ± 0.25 µm; FPF(3.3) and FPF(5.8) were approximately 50% and 90%, respectively, for all nebulizers. CONCLUSION: Although all nebulizers appeared acceptable to deliver micafungin to the lungs, the Pari LC Star had the smallest MMAD and highest FPF(3.3) and FPF(5.8). These properties of the Pari LC Star should result in greater delivery of the aerosol to the lungs. Additional research on pulmonary delivery and clinical tolerability is warranted.
