Dispersion and Size Distribution of Amiloride by Metered Dose and Dry Powder Inhalers

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Abstract
An aerosol of amiloride, nebulized from liquid solution, shows promise as treatment for viscous secretions in the airways of patients with cystic fibrosis. To improve ease of delivery and perhaps pharmacokinetics of amiloride aerosol, we examined two devices that generate dry powder aerosols: (a) the Spinhaler and (b) the metered dose inhaler (MDI). We estimate that treatment will require generation of 8 to 12 mg/day of respirable particles (<4.7um) to achieve the desired concentrations of drug in the conducting airways. However, oropharyngeal deposition of the drug must be minimized because excessive diuresis or hyperkalemia may develop if the total systemic dose to the patient exceeds 20 mg/day. The Spinhaler was tested alone and in combination with an impactor designed to reduce the mass of large particles deposited in the oropharynx. The MDI was attached to a spacer and studied with and without the same impactor. An Andersen cascade impactor was used to determine the aerodynamic size distribution of the amiloride generated by both devices. The collected amiloride was analyzed by spectrophotometry. We achieved generation of 12 mg/day of respirable amiloride without exceeding a total systemic dose of 20 mg/day using the Spinhaler with the impactor, and by the MDI, spacer, and impactor. Generation of 8 mg/day of respirable amiloride without exceeding a daily systemic dose of 20 mg/day was achieved using the MDI and spacer.