(7) A variety of reasons may exist for the selleck products disconnect between real-world usage of inhaled antibiotics and recommendations in the treatment guidelines. Time burden is an important factor in chronic diseases like CF. These patients may be required to administer many daily chronic inhaled therapies, including bronchodilators, mucolytics, hypertonic saline, and inhaled antibiotics. These aerosol treatments, added to airway clearance maneuvers, take patients an average of almost 2h to complete.(8) TIS is administered twice daily with the PARI-LC? PLUS or comparable jet nebulizer (with a suitable compressor) over a period of 15�C20min.(9) Aztreonam for inhalation solution is administered with an electronic vibrating mesh nebulizer (Altera?; Pari Innovative Manufacturers, Inc., Midlothian, VA, USA).

The solution only takes 2�C3min to inhale, and is administered three times a day versus twice a day for TIS. Furthermore, both aztreonam inhalation solution and colistimethate must be reconstituted immediately before nebulization, increasing the handling time and delivery complexity for these antibiotics. All nebulizers require regular cleaning after each use to prevent bacterial contamination and to ensure that the performance of the device is not compromised. This is a time-consuming process, and many patients do not clean their nebulizer as directed.(10) In addition to the time burden, nebulizer/compressor combinations are noisy, bulky, and require a power source. Furthermore, tobramycin and aztreonam inhalation solutions must be stored in a refrigerator, decreasing convenience.

The ability to deliver therapeutic doses of antibiotics with a portable inhaler in a fraction of the time required for the entire process of nebulization would be a significant advance that may improve patient compliance and clinical outcomes.(9) The principal reason that nebulizers have been utilized for aerosol delivery of anti-infectives lies in the high lung doses required for effective treatment. For example, the lung dose for TIS is approximately 35mg.(11) Recent developments in particle engineering, in particular the development of PulmoSphere? technology, has enabled the delivery of a large amount of dry powder (up to 25mg) to the lungs in a single actuation.

(12) Early development of dry powder antipseudomonal antibiotic formulations Traditional formulation approaches for producing dry powders for inhalation have relied on ��top-down�� manufacturing Dacomitinib methods, where large crystalline drug particles are milled (micronized) to produce fine crystals with a median diameter suitable for inhalation (i.e., 1�C5��m). The micronization process is analogous to throwing a crystal ball against a steel wall. The crystal shatters into millions of pieces, with a broad particle size distribution and limited control of particle morphology.