Nebulized Mannitol, Particle Distribution, and Cough in Idiopathic Pulmonary Fibrosis

Respiratory Care
Pooja M KanthGerald C Smaldone

Abstract

Inhaled interferon, a potential treatment for idiopathic pulmonary fibrosis, must be formulated with mannitol, which can cause bronchospasm and cough. Coughing during drug inhalation can be affected by many factors, but some factors are fixed by the needs of the formulation and inflammatory disease in the airways. A component of the cough response may be related to sites of deposition, particularly upper and central airways. If deposition sites are important, then manipulating the particle distribution of the aerosol may mitigate coughing. To design a therapeutic formulation and delivery system for formulations that contain mannitol, we tested the effect of particle distribution on cough during mannitol inhalation in volunteers with idiopathic pulmonary fibrosis. A solution of mannitol was formulated to match requirements for future interferon formulations (40 mg/mL, 220 mOsm/L). Mannitol aerosols were generated by using different nebulizers providing particle distributions that were expected to vary upper airway deposition. The nebulizer fill volume was adjusted to correct for differences in nebulizer efficiency with a target inhaled mass of 20 mg. Particle distributions were measured by cascade impaction (mass median aerodyna...Continue Reading

Citations

Dec 20, 2019·Journal of Aerosol Medicine and Pulmonary Drug Delivery·Joshua Samuel, Gerald C Smaldone
Jul 16, 2020·British Journal of Pharmacology·Rachel Yoon Kyung ChangHak-Kim Chan

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