In vitro deposition properties of nebulized formoterol fumarate: effect of nebulization time, airflow, volume of fill and nebulizer type

ABSTRACT

Objective: The aim of this study was to investigate in vitro the delivery of a new long-acting β₂-agonist (LABA) drug formoterol fumarate inhalation solution (20 µg/2 mL) nebulized with and without ipratropium bromide (0.5 mg/2.5 mL) at different administration times (2.5–22.5 min), airflows (5–28.3 L/min), nebulizer fill volumes (2–6 mL), and nebulizer brands (Pari LC+, Ventstream and DeVilbiss).

Method: Formoterol fumarate with and without ipratropium bromide was aerosolized at different administration times, airflows, nebulizer fill volumes, and nebulizer brands. The drug deposited on the throat, filter and stage plates was collected and analyzed by HPLC to determine the aerodynamic profiles of the nebulized drugs under each variable.

Results: In addition to altering the aerosol characteristics, increasing the nebulizer fill volume including the addition of ipratropium bromide produced a significant (p < 0.05) increase in the drug output. As expected, sputtering time was significantly longer at low airflows, and vice versa at higher airflows but with a significant loss of drug delivered presumably due to greater solvent evaporation at higher airflows. Airflows between 10 and 28.3 L/min and a nebulization time of approximately 10 min appear sufficient for producing aerosols within the respirable range (1–5 µm MMAD) with the nebulizer/compressor combination used. While the drug output varied significantly (p < 0.05) among the three brands of nebulizers tested, the LC+ nebulizer appears to produce aerosols (2.7 ± 0.1 µm MMAD) capable of penetrating more deeply into the lung than the other nebulizers evaluated under the current test conditions. This study did not attempt to evaluate different nebulizer/compressor combinations. Also, the cascade impaction data may not necessarily reflect aerosol deposition in the airways in vivo, which may be different depending on the health status of the patient.

Conclusion: The results demonstrated that administration of nebulized formoterol fumarate require proper selection of a delivery system/method for safe and effective therapy of the medication with and without ipratropium bromide.

Key words: :

• Admixture
• Aerosol particle size distribution
• COPD
• Formoterol fumarate
• Nebulizer

Acknowledgments

Declaration of interest: This study was supported by Dey LP, Napa, CA, USA. The authors thank the clinical, medical, and marketing groups at Dey for their useful contribution during the course of this study. All the authors are full time employees of Dey.