tudy of the technological parameters of ultrasonic nebulization ABSTRACT  The principle of an ultrasonic nebulizer is based on the vibrations of a piezoelectric crystal driven by an alternating electrical field. These periodic vibrations are characterized by their frequency, their amplitude, and their intensity, which

corresponds to the energy transmitted per surface unit. When the vibration intensity is sufficient, cavitation occurs, and droplets are generated. Ventilation enables airflow to cross the nebulizer and to expel the aerosol droplets. For a given nebulizer, the vibration frequency of the piezoelectric crystal is fixed, often in the range 1–2.5 MHz. In most cases, an adjustment in vibration intensity is possible by modifying vibration amplitude The ventilation level is adjustable. The vibrations may be transmitted through a coupling liquid—commonly water—to a nebulizer cup containing the solution to be aerosolized. In this work, we studied the influence of the technological parameters of ultrasonic nebulization on nebulization quality. Our study was carried out with a 9% sodium chloride solution and a 2% protein solution (1 protease inhibitor). Three different ultrasonic nebulizers were used. An increase in vibration frequency decreased the size of droplets emitted. The coupling liquid absorbed the energy produced by the ultrasonic vibrations and canceled out any heating of the solution, which is particularly interesting for thermosensitive drugs. An increase in vibration intensity did not modify the size of droplets emitted, but decreased nebulization time and raised the quantity of protein nebulized, thus improving performance. On the other hand,an increase in ventilation increased the size of emitted droplets and decreased nebulization time and the quantity of protein nebulized because more drug was lost on the walls of the nebulizer. High intensity associated with low ventilation favors drug delivery deep into the lungs. 70603

INTRODUCTION

    The principle of an ultrasonic nebulizer is based on the vibrations of a piezoelectric crystal (transducer) driven by an alternating electrical field.Ultrasounds are sound waves with a frequency higher than 20,000 Hz (1,2).

    A sound wave is a periodic disturbance in a material medium in which the molecules in certain regions are momentarily displaced from their equilibrium positions and experience a compensating force because of the elasticity of the medium. This force is responsible for propagating the disturbance wave in the form of an oscillation of the molecules around their mean position, and its magnitude influences the velocity with which the wave is propagated.

    The propagation of sound waves through the medium involves alternating positive and negative deviation from the mean values of density, pressure,temperature, particle velocity, and particle acceleration.If the pressure amplitude is sufficiently high and causes great changes in pressure, a very significant effect called cavitation takes place, which is the

formation and collapse of small bubbles in the liquid. The formation is related to the negative pressure portion of the sound waves, which causes some of the vapor in the liquid to come out of the solution in the form of minute bubbles. These bubbles then act as weak spots for the further tearing apart

of the liquid to form larger cavities.

    Then, when the pressure becomes positive, in the other half of the sound wave cycle, the cavities collapse with a violent hammering action that generates high local instantaneous pressures and temperature.During the implosion of the bubbles, the instantaneous particle velocities reach supersonic speed, and a tiny shock wave is produced, resulting in a water geyser at the surface. Periodic hydraulic shocks set the surface of the liquid into vigorous oscillatory motion, with the formation of standing capillary waves of finite amplitude on its surface and the spontaneous excitation of the standing capillary wave.