Influence of the technological parameters of ultrasonic nebulisation on the nebulisation quality of α1 protease inhibitor (α1PI)

Abstract

The principle of an ultrasonic nebuliser is based on the vibrations of a piezo-electric crystal driven by an alternating electrical field. These periodical vibrations are characterised by their frequency, their amplitude and their intensity which corresponds to the energy transmitted per surface unit. When the vibration intensity is sufficient, cavitation appears and generates droplets. Ventilation enables an airflow to cross the nebuliser and to expulse the aerosol droplets. For a given nebuliser, the vibration frequency of the piezo-electric crystal is fixed and is often in the range of 1–2.5 MHz. In most cases, an adjustment in vibration intensity is possible by modifying vibration amplitude. The ventilation level is adjustable. The influence of these two parameters on the efficiency of ultrasonic nebulisation is studied. The study was carried out with a protein solution that had to be administered into the lungs. The solution used presented a viscosity of 1.25 mPa and a surface tension of 53 mN/m. The integrity of the protein was checked which was submitted to different vibration conditions. Nebulisation efficiency was evaluated by determining droplet size, the percentage of drug nebulised and nebulisation time. An increase in vibration intensity does not modify the size of droplets emitted, but decreases nebulisation time and raises the quantity of protein nebulised, thus improving performance. On the other hand, an increase in ventilation increases the size of droplets emitted, decreases nebulisation time and the quantity of protein nebulised because more drug is lost on the walls of the nebuliser. High intensity associated with low ventilation favours drug delivery deep into the lungs.