Optimizing the in vitro performance of Respimat.

Aerosolization of a drug solution in a handheld device for inhalation therapy can be achieved either by vibration or extrusion through a fine nozzle. The latter method does not necessitate the use of an electrical power source and has been developed further in Respimat. The device was adapted for mass production, selecting appropriate materials for the desired size and weight as well as for stability and technical performance. After optimization of the nozzle design, Respimat produced encouraging results in its first lung deposition study in volunteers compared with a chlorofluorocarbon-driven metered dose inhaler (CFC-MDI). Respimat is a reusable device with a mode of action that differs from those of other inhalers. The mechanical power from a coiled spring forces a metered volume of drug solution through a nozzle in a unique component, the uniblock. The convergence of two fine jets of liquid generates a slow-moving aerosol of soft mist. The fine particle fraction in the aerosol, determined from experiments with the Anderson Cascade Impactor (Anderson Instruments, Inc., Smyrna, GA), is approximately 66% for an aqueous drug solution and 81% for an ethanolic solution. This value is about 2.5 times higher than the fine particle fractions determined for CFC-MDIs, and the velocity is about five times lower (e.g., 10 m/s for an aqueous solution), with both factors contributing to the improved lung deposition. In addition, the dose release duration from Respimat is considerably longer than that from CFC-MDIs at approximately 1.2 seconds, allowing more time for the patient to coordinate actuation and inspiration. The reliability and consistency of dose delivery from Respimat also have been confirmed.