1998 OPEN FORUM Abstracts
MDI Aerosol Delivery... The Science
Richard Dalby, PhD
The modern MDI contains a drug, one or more propellants, and in most cases, a surfactant. The liquefied propellant serves as an energy source to expel the formulation from the valve in the form of rapidly evaporating droplets, and as a dispersion medium for the drug and surfactant. Hydrofluoroalkane 134a has emerged as the primary replacement for chlorofluorocarbon propellants. The surfactant lubricates the metering valve mechanism, and helps disperse micronized drug particles. Drug dissolution usually necessitates the addition of less volatile ethanol. Flavors and sweeteners may be present to combat the unpleasant taste associated with significant oropharyngeal deposition.
(See original for figure)
With the exception of Azmacort(r) and Breathaire(r), all MDIs are supplied with a molded plastic actuator which positions the patient's lips very close to the spray orifice (if they use the closed mouth method). This provides a short distance between the spray orifice and oropharynx, and necessitates excellent coordination between actuation of the MDI and inhalation by the patient to avoid oropharyngeal deposition. Spacer devices increase this distance, allowing the rapidly advancing aerosol cloud to decelerate before reaching the throat. This makes perfect synchronization between actuation and inhalation slightly less important. In addition, spacers allow more time for propellant evaporation, resulting in the formation of smaller droplets or particles, and less reflex coughing and exhalation due to local cooling of the throat by impacted, evaporating droplets. A large proportion of drug that would otherwise deposit in the oropharynx is retained in a spacer. This reduces systemic drug levels and minimizes local side effects and bad tastes in the mouth.
Spacers are essentially hollow tubes through which a patient should have started inhaling prior to actuating their MDI. They are designed to empty in a single inhalation. Holding chambers are typically larger in volume, frequently conical-shaped, and are designed to facilitate drug delivery even when a patient actuates their MDI just before or after inhalation. Their larger size is designed to reduce drug losses on the interior wall due to impaction and sedimentation. Holding chambers contain a one way valve to prevent an inadvertent exhalation from flushing a previously aerosolized dose from the device. Delays between actuation and inhalation, making multiple actuations in the reservoir, and emptying the reservoir over several inhalations all reduce the efficiency of aerosols delivery to the lung.
Larger spacers and holding chambers more effectively enhance lung delivery compared to smaller ones. Because they are inconvenient to carry collapsible designs are common (Inspirease(r)). Other designs direct the emerging aerosol spray in the opposite direction to the inhaled airstream in an attempt to increase the flight time while minimizing device size (Aerosol Cloud Enhancer(r), Inspirease(r), OptiHaler(r)) Holding chambers may also contain flow restrictors to control the patients inhalation rate, and have mechanisms to coordinate inhalation with MDI actuation (OptiHaler(r)). Many audibly warn the patient when they are inhaling too fast (Aerosol Cloud Enhancer(r), AeroChamber(r), Inspirease(r), Optichamber(r)) Newer devices are typically transparent to encourage regular cleaning and some are designed to fit into ventilator circuits. Because spacers and holding chambers are often designed to fit multiple MDIs (which may have significantly different compositions, valves and actuators), their ability to equally enhance the delivery of drug from all MDI products has been questioned.
The 44th International Respiratory Congress Abstracts-On-Disk®, November 7 - 10, 1998, Atlanta, Georgia.