Pre-Clinical Testing of Aerosolized Inhaled Milrinone Using a Vibrating Mesh Nebulizer

Purpose Inhaled milrinone (MIL) has been used empirically to reduce pulmonary vascular resistance and improve right ventricular dysfunction without systemic adverse effects; however characterization of this process is not reported in the literature. We sought to characterize aerosolized MIL particle size, nebulization degradation profile, and quantification of drug delivery using a vibrating mesh nebulizer connected to a mechanical ventilator circuit in preparation for a human heart failure clinical trial. Methods and Materials Mass Spectrometry was performed on nebulized MIL samples and saline controls. A pharmaceutical grade impactor was used for aerodynamic particle size studies. High pressure liquid chromatography (HPLC) was used to determine final mass median aerodynamic particle size (MMAD), geometric standard deviation (GSD), and fine particle fraction (FPF). Nebulized MIL recovered at the end of an endotracheal tube (ETT) in a mechanical ventilator circuit was quantified using HPLC. All studies were performed in triplicate. Results Mass Spectrometry did not reveal MIL degradation products or formation of new drug compounds. Aerodynamic MMAD for nebulized MIL followed a Gaussian curve distribution. [ figure 1 ] MMAD = 4.22 μm with GSD = 2.29 μm and FPF = 0.62 +/− 0.7. 22.9% of nebulized MIL was recovered at the end of the ETT. Conclusions Nebulizing MIL using a vibrating mesh nebulizer attached to a mechanical ventilator circuit is feasible, results in delivery of a consistent unaltered drug product, and generates a respirable aerosol with size properties ideal for both pulmonary and systemic drug delivery.