Innovations and perspectives of metered dose inhalers in pulmonary drug delivery.

The phase-out of chlorofluorocarbons (CFCs) has spurred the development of alternative pulmonary drug delivery systems to pressurized metered dose inhalers (MDIs), such as dry powder inhalers and pocket size nebulizers. Reformulation of CFC-MDIs with hydrofluoroalkanes (HFAs) 134a and 227 is also an opportunity to improve these widely accepted systems with respect to ease of handling, compliance, dosing, and more reliable and efficient lung deposition. MDIs have the advantage to protect the drug substance from external parameters such as temperature and humidity and to meter and de-agglomerate the drug independent from patients inspiratory flow rates. Novel formulation technologies combined with improved valves and actuators should help to overcome dose uniformity and priming problems and will increase the percentage of fine particles capable of reaching the deeper regions of the lungs. Spacer mouthpieces can reduce the cold freon effect and undesired oropharyngeal deposition caused by the rapid evaporation of the propellant and plume velocity of the aerosol cloud. More advanced delivery devices may allow the patient to inhale at predetermined flow rates (fast/slow) to target the deposition of fine drug particles (1-6 microm) to specific sites into the lungs. Breath-actuated devices make these systems more effective and patient friendly. The above features in combination with numerical counters showing the remaining number of shots, and built-in blocking mechanisms to avoid tail-off dependent dose uniformity problems of the last labeled shots, should help to improve both acceptance and compliance of pMDIs compared to other inhalation devices. However, only those inhalation systems, which are accepted and appreciated by patients and offering an ambulatory treatment at reasonable cost, will be successful in a more and more competitive market. These issues must be considered in the development of future devices and formulations.