Nebulizers

Medical nebulizers can be divided into two main groups, pneumatic and electric. A pneumatic generator operates from a pressurized gas source, while an electric generator derives its power from an electric source. There are two types of pneumatic nebulizers (jet and hydrodynamic) and one electric generator (ultrasonic) presently used for medical purposes.

The jet nebulizer is a system in which a high-velocity gas flow is directed over a tube that is immersed in a water reservoir (Figure 10.8). The expansion of the driver gas decreases the pressure over the tube, which draws the formulation into the gas stream. The high shear rate in the jet stream then nebulizes it. The hydrodynamic nebulizer uses a system that prepares a film of water for aerosol formation by flowing it over a hollow sphere. A small orifice in the sphere expels gas at supersonic velocity. This high-velocity gas ruptures the thin film of water and produces a continuous dispersion of fine, liquid particles. A gas cylinder or compressor supplies the gas pressure. The ultrasonic nebulizer consists of a piezo-electric crystal which produces high frequency sound waves in the liquid in the nebulizing unit. The surface waves produce small droplets (Faraday crispations) which are conducted away by an airstream for inhalation. All these devices produce relatively broad droplet size distributions in which a large fraction of coarse droplets are present. Consequently most use some sort of baffle system in the airstream; coarse droplets impact on this and are returned to the reservoir for re-nebulization, while the smaller particles avoid the baffle and are passed to the patient.

The properties of nebulizers vary widely; while all produce droplets with sizes in the range 1-10 pm, they vary significantly in droplet size distribution and pulmonary deposition12 13. Despite this they have a number of advantages that is causing a renewal of interest in their use. Because MDIs and DPIs have a relatively high gas flow rate, they show high oropharyngeal impaction. This problem is reduced in nebulizers since the airflow can be adjusted to suit the patient's inhalation rate. Continuous nebulization can deliver very large quantities of drugs if necessary, from aqueous solutions without major formulation

Air Kntrainmcnt

Air Kntrainmcnt

Figure 10.8 An air-driven nebulizer

problems. Unfortunately most nebulizers are bulky and require a fixed power source, which limits their use severely.

In order to combine these advantages of nebulizers with the portability of MDIs, Boehringer Ingelheim have developed the Respimat®, a spring-driven spray with a similar outward appearance to a conventional MDI. Unlike an MDI, the Respimat® delivers its spray in a slow low-velocity cloud. This leads to increased central pulmonary deposition14, which is probably due to the increased time available for droplet evaporation before inhalation, and the reduced plume velocity, which reduces oropharyngeal impaction. Since these two factors are the main reasons for the success of spacer devices (see below), the addition of a spacer to a Respimat® caused no significant improvement in deposition.

Spacer devices and ancillary equipment

A number of techniques have been used in an attempt to improve the deposition of inhaled drug particles. The best known of these are the various kinds of spacers, chambers which are placed between the inhaler device and the patient's mouth (Figure 10.9). These devices cause considerable improvements in the fraction of dose deposited in the lungs and operate through a number of mechanisms. Firstly they provide a delay time before inhalation to allow full evaporation of propellant, so that the particles have reached their minimum size. Secondly they slow down the particle cloud so that the impaction velocity on the oropharynx is reduced, thus reducing impaction in this region. Finally they have a reservoir function which makes the timing of inhalation by the patient less critical. A typical example of such a device is the Nebuhaler®, which was studied by Thorsson et al for the delivery of budenoside. The Nebuhaler® caused a significant increase (from 12% to 38%) in pulmonary deposition, and an improvement in peripheral deposition. When assessing studies of such devices, it is important to realize that the spacer itself acts as an impaction filter and a proportion of the larger droplets are removed by it. In addition plastic devices accumulate wall charges and act as electrostatic precipitators, causing significant drug losses which vary with handling, humidity and cleaning or priming history15.

Several methods have been developed to fire the aerosol device when the patient's breathing is correctly timed. We have already mentioned the Autohaler® which is fired by a pressure switch. More recent devices such as the SmartMist® and AERx® add the sophistication of microprocessor control so that usage can be logged and the device can be controlled with a degree of sophistication16 17.

Metered Dose

Inhaler +

Adaptor t

Mouthpiece

Mouthpiece

Adaptor

Cham bet

Figure 10.9 A typical spacer device

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