Assessment of recent nebulizer delivery systems using urinary pharmacokinetics method and aerodynamic characteristics of TOBI (R) nebulized dose following inhalation

作者：Mashat M^*; Clark B J; Assi K H; Chrystyn H

来源：Journal of Drug Delivery Science and Technology, 2017, 39: 428-434.

DOI：10.1016/j.jddst2017.04.007

• Lung bioavailability
• Urinary pharmacokinetics
• CEN (Committee European de
• Normalization) method
• Tobramycin
• Inhalation
• Nebulizer

Background: Chronic infections with Pseudomonas aeruginosa are a leading cause of morbidity in patients with cystic fibrosis (CF). Tobramycin nebulizer solution (TNS) is indicated for maintenance therapy in CF patients. TOBI is a tobramycin nebulizer solution (TNS) approved by FDA for maintenance therapy for patient with CF. Adherence to recommended therapy in CF has always been a challenge and new generation nebulizers are increasingly used "off label" to reduce the time required for inhalation, potentially improving patient compliance.
Objectives: To assess the performance of selected recent nebulizer delivery systems for determination the optimum combinations to deliver TOBI. Using the relative lung bioavailability of TOBI to the lungs in healthy volunteers, following inhalation from selected nebulizer delivery systems, using a urinary pharmacokinetics method. In vitro aerodynamic characteristics of the nebulized dose were also determined.
Methods: Serial urine samples were collected from 12 healthy volunteers up to 24 h post -inhalation of TOBI inhaled solution following delivery by Pari LC Plus, Sidestream, NE-U22-E Omron and Aeroneb Go nebulizers. In vitro aerodynamic characteristics of the nebulized dose were also determined according to the CEN (Committee European de Normalization) method.
Results: The mean (SD) relative lung bioavailability from Pari LC Plus, Sidestream, Omron, and Aeroneb Go nebulizers was 4.9 (0.5), 3.9 (0.5), 7.1 (1.3), and 7.7 (0.7) %, respectively. The mean (SD) mass median aerodynamic diameter (MMAD) of the drug particles from the same systems was 2 (0.2), 2 (0.2), 1.2 (0.03) and 2.0 (0.1) Itm, and the corresponding fine particle doses (FPD) were 2.2 (0.23), 1.5 (0.2), 3.44 (0.3) and 2.8 (0.3) mg.
Conclusion: The data obtained from in-vitro and in-vivo studies reflect poor relative lung bioavailability of tobramycin following jet nebulization.

• 出版日期2017-6