Controlling the droplet size of formulations nebulized by vibrating-membrane technology

•Membranes of the Aeroneb® Pro and eFlow®rapid differ in composition and morphology.•Nozzle design was of minor impact on the process of atomization.•Conductivity and viscosity affected the aerodynamic diameter of generated aerosols.•Excipients rendering multiple formulation parameters are of special interest.•Both nebulizer units are qualified for the production of respirable aerosols.

Manipulation of aerosol characteristics is of special interest for pulmonary therapy, as a suitable particle size optimizes pulmonary deposition. The present study investigated the impact of formulation variables on the aerodynamic particle diameter (da) when nebulized by vibrating-membrane technology.Membranes implemented in the Aeroneb® Pro and eFlow®rapid nebulizer revealed difference in metal composition and nozzle morphology as determined by energy dispersive X-ray measurements and scanning electron microscopy. Laser diffraction analysis of generated aerosol droplets identified the conductivity and dynamic viscosity of formulations as parameters with significant influence on the da for both nebulizers. Accordingly, sample supplementation with particular excipients (conductivity: >50 μS/cm, dynamic viscosity: >1.5 mPa s) facilitated a reduction of the da from ⩾8 μm, which is clearly in conflict with inhalative drug delivery, to respirable da as small as ∼3 μm.Overall, controlling the da of formulations nebulized by vibrating-membrane technology seems to be technical feasible by an adequate adaption of samples’ physicochemical properties. The Aeroneb® Pro and eFlow®rapid device are both qualified for the production of respirable aerosol clouds from specified formulations.

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