New liquid aerosol generation devices: systems that force pressurized liquids through nozzles

Over the past few decades, aerosol delivery devices have been relatively inefficient, wasteful, and difficult for patients to use. These drawbacks have been tolerated because the drugs available for inhalation have wide therapeutic margins and steep dose-response curves at low doses. Recently several forces have converged to drive innovation in the aerosol device industry: the ban on chlorofluorocarbon propellants in metered-dose inhalers, the need for more user-friendly devices, and the invention of expensive inhalable therapies for topical and systemic lung delivery. Numerous devices are in development to improve the efficiency, ease of use, and reproducibility of aerosol delivery to the lung, including systems that force liquid through a nozzle to form the aerosol cloud. The Respimat is a novel, compact, propellant-free, multi-dose inhaler that employs a spring to push drug solution through a nozzle, which generates a slow-moving aerosol. Deposition studies show that the Respimat can deliver 39-44% of a dose to the lungs. Clinical asthma and chronic obstructive pulmonary disease trials with bronchodilators show that the Respimat is 2-8 times as effective as a metered-dose inhaler. Respimat has been tested with bronchodilators and inhaled corticosteroids. The AERx device uses sophisticated electronics to deliver aerosol from a single-dose blister, using an integral, disposable nozzle array. The electronics control dose expression and titration, timing of aerosol generation with the breath, and provide feedback for proper inhalation technique. Lung deposition ranges from 50 to 80% of the loaded dose, with remarkable reproducibility. AERx has been tested with a variety of drugs, for both topical and systemic delivery, including rhDNase (dornase alfa), insulin, and opioids. These novel devices face competition from other technologies as well as financial and regulatory hurdles, but they both offer a marked improvement in the efficiency of pulmonary drug delivery.