Abstract
Nebulizers have a number of advantages for the delivery of inhaled pharmaceutical aerosols, including the use of aqueous formulations and the ability to deliver process-sensitive proteins, peptides, and biological medications. A frequent disadvantage of nebulized aerosols is poor lung delivery efficiency, which wastes valuable medications, increases delivery times, and may increase side effects of the medication. A focus of previous development efforts and previous nebulizer reviews, has been an improvement of the underlying nebulization technology controlling the breakup of a liquid into droplets. However, for a given nebulization technology, a wide range of secondary devices and strategies can be implemented to significantly improve lung delivery efficiency of the aerosol. This review focuses on secondary devices and technologies that can be implemented to improve the lung delivery efficiency of nebulized aerosols and potentially target the region of drug delivery within the lungs. These secondary devices may (1) modify the aerosol size distribution, (2) synchronize aerosol delivery with inhalation, (3) reduce system depositional losses at connection points, (4) improve the patient interface, or (5) guide patient inhalation. The development of these devices and technologies is also discussed, which often includes the use of computational fluid dynamic simulations, three-dimensional printing and rapid prototype device and airway model construction, realistic in vitro experiments, and in vivo analysis. Of the devices reviewed, the implementation of streamlined components may be the most direct and lowest cost approach to enhance aerosol delivery efficiency within nonambulatory nebulizer systems. For applications involving high-dose medications or precise dose administration, the inclusion of active devices to control aerosol size, guide inhalation, and synchronize delivery with inhalation hold considerable promise.