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tion formulations of drugs can be developed for nebu- lization, have led to a number of largely overlooked opportunities for nebulization as a means of delivering drugs. This article will highlight some of these opportu- nities and the reasons they have come about. Nebulizer technology Nebulizer technology available to patients today consists of jet, mesh and, to a lesser extent, ultrasonic nebulizer devices (Figure 1). Of these, the most widespread is the jet nebulizer, which relies on a source of compressed air to create a respirable aerosol. Nonetheless, the conven- tional jet nebulizer also has disadvantages. Bulky size, the requirement for a grid-connected power supply and noisy operation lasting 6 to 15 minutes for a fill of 2 to 5 mL of liquid for each treatment are significant consider- ations for the patient, compared with one or two puffs taken from a DPI or pMDI. Treatments can add up to a significant burden upon a patient's free time and quality of life, and the requirement to carry a bulky compressor and associated leads and tubing may not fit well with the active lifestyles of many patients. Ultrasonic nebulizers that generate aerosol by means of focused ultrasonic waves within the nebulizer liquid (Figure 1) improved the size and noise issues inherent in jet nebulizers, but were associated with additional disadvantages, such as inefficient nebulization of suspensions and heating of medication during nebulization that could damage ther- molabile drugs. Both jet and ultrasonic nebulizers are also inefficient, continuing to generate and thereby wast- ing aerosol while a patient is exhaling. The efficiency of jet nebulizers has been improved slightly with the intro- duction of breath-enhanced models that boost output during the inhalation phase of breathing. In addition, breath-activated jet nebulizers provide even higher effi- ciency, but with increases in nebulization time and reduced applicability. Their use should be confined to older children and adults to ensure sufficient inspiratory force to activate the mechanism. 13 Despite such improvements, these nebulizers still retain approxi- mately 1 mL of the medication at the end of treatment, which will go to waste. All of these issues have led to the nebulizer becoming the least common of the three main delivery technologies (nebulizer, pMDI and DPI) used to deliver aerosol therapy. However, the most significant of these disadvantages are now being addressed with the increasing adoption of mesh nebulizers, which offer battery-operated portabil- ity and rapid, quiet operation. In mesh nebulization, medication is aerosolized in a single pass through the mesh (Figure 1) without needing classification via the baffles used in jet and ultrasonic nebulizers, which return oversize aerosol droplets to the medication reservoir. This can result in greater efficiencies in time, energy expenditure and volume delivered. The latest generation of mesh nebulizer can be expected to operate with treat- ment times of around 4 minutes and residual volumes of about 0.3 mL. 14 Improvements in the manufacturing process include the optical assessment of meshes to ensure that particle sizes and treatment times the patient experiences are consistent, even after replacement of the mesh. 15 Treatment burden can be further reduced, as the new generation mesh of nebulizers can be expected to be easier to use and clean. 16 Ease of cleaning may be partic- ularly relevant to mesh nebulizers, as treatment time may be prolonged due to blockage of some nozzles if the Schematic representations of nebulization via jet, ultrasonic and mesh nebulizers Figure 1 Jet nebulization Aerosol generated by the breakup of a fast moving air/liquid mix- ture; larger droplets impact on baffles and are returned to the bulk fluid; smaller droplets exit the nebulizer for inhalation. Aerosol generated at the peak of a fountain created by focused ultra- sonic waves; larger droplets impact on baffles and are returned to the bulk fluid; smaller droplets exit the nebulizer for inhalation. Aerosol generated when columns of fluid are extruded from small mesh holes and break up to form aerosol droplets; droplet size is related to hole size; droplets exit the nebulizer for inhalation. Ultrasonic nebulization Mesh nebulization 10 JUNE2017 Inhalation