Heated nebulization of ambroxol hydrochloride: engineering submicron aerosols for pulmonary drug delivery

Chronic respiratory diseases (CRDs) remain challenging to treat, largely due to the difficulty in delivering therapeutic agents to the deep lung. Ambroxol hydrochloride (AH), a widely used mucolytic agent that promotes mucus clearance, is indicated for conditions such as asthma, emphysema, and chronic bronchitis. This study reports the in vitro characterization of a heated medical nebulizer (MD6-HA20-2) for the generation of AH inhalable aerosols. The device vaporizes a liquid AH formulation via a battery-operated heating element; upon inhalation, the vapor condenses into aerosols exhibiting a mass median aerodynamic diameter of 0.53 ± 0.06  µm (GSD = 1.26). Across 200 consecutive inhalation actuations, the nebulizer delivered 25.21 ± 0.06 µg of AH per actuation with an atomization efficiency of 99.66 ± 0.47%, confirming highly reproducible dosing. High-performance liquid chromatography verified the thermal stability of AH throughout the nebulization process, and analysis of carbonyl compounds and trace toxic metals in the aerosol indicated that exposures to potentially harmful by-products remained below established health-based benchmarks. Collectively, these in vitro findings demonstrate that the heated nebulization platform can reliably generate submicron AH aerosols with a favorable preliminary chemical safety profile, supporting its continued development for pulmonary drug delivery.