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

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 (d(a)) 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 d(a) for both nebulizers. Accordingly, sample supplementation with particular excipients (conductivity: >50 μS/cm, dynamic viscosity: >1.5 mPa s) facilitated a reduction of the d(a) from ⩾8 μm, which is clearly in conflict with inhalative drug delivery, to respirable d(a) as small as ~3 μm. Overall, controlling the d(a) 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.