Study 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 in tensity 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 1-2.5MHz. 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 (alpha1 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.

Vibrating Sharp‐edge Spray Ionization (VSSI) for voltage‐free direct analysis of samples using mass spectrometry

“…The vibration of the glass slide is induced by applying a radiofrequency (RF) signal to a piezoelectric transducer working at the natural frequency of the system (~97 kHz). It is not uncommon to observe mechanical vibration induce the aerosolization of liquids as demonstrated in many types of ultrasonic nebulizers 20–22 . For ultrasonic nebulizers, the interaction between acoustic waves and liquid generates capillary wave and cavitation effects on the liquid–gas interface, which subsequently causes the detachment of liquid droplets from the body of the fluid.…”

Ultrasonic nebulization platforms for pulmonary drug delivery

“…Physically, the rim of the collapsing bubble is stretched radially downward and initially outwards, and subsequently inwards, under the action of capillarity ( Figure 2A--C), until it contracts on itself to form an elongated thread that eventually pinches off to form an aerosol droplet ( Figure 2D, E). If these violent and transient collapse events near the interface occur simultaneously and periodically, finite amplitude standing capillary waves are excited on the interface [45] that destabilize beyond a critical vibration threshold to produce simultaneous pinch-off events along the interface. Mechanisms that describe the formation of the droplet from the break-up of interfacial capillary waves [46][47][48] have been discussed in various articles [49][50][51].…”

Surface active drugs significantly alter the drug output rate from medical nebulizers

“…Cavitation theory proposes that a piezoelectric crystal, operating at low frequencies, vibrates the bulk liquid causing the formation of cavitation bubbles. The bubbles are formed due to the negative pressure of the sound waves which causes some vapor in the liquid to come out of the solution in the form of bubbles (Flament et al, 2001). As the air bubbles, which have a short life span, rise towards the air-liquid interface, the internal pressure of the cavitation bubbles equilibrates with the atmosphere, causing the bubbles to implode.…”