Metered dose inhalers, pressurized spacer devices

Newman, S.P., Clark, A.R., Talaee, N., and Clarke, S.W., Pressurized aerosol deposition in the human lung with and without an open spacer device. Thorax, 44 706-710 (1989). Newman, S.P., Clark, A.R., Talaee, N., and Clarke, S.W., Lung deposition of 5 mg Intal from a pressurized metered dose inhaler assessed by radiotracer technique, Int. J. Pharm., 74 203-208 (1991). 

Metered dose inhaler has been the most popular aerosol delivery device for the treatment of respiratory diseases, which is attributable to its portability and simple operation. Although seemingly easy to use, the MDI is a sophisticated device in design. The drug(s) are suspended or dissolved in a liquefied propellant system, which may also contain excipients such as cosolvents or surfactants. The formulation is kept pressurized in a small canister, sealed with a metering valve. Upon actuation through an actuator, the valve opens and the metered dose is dispensed as an aerosol spray from the expansion and vaporization of the propellant under ambient pressure. The inhalers may be used alone or with spacer devices, the electrostatic issues of which are considered in a later section. The present discussion focuses on the inherent charging of particles produced from MDIs. 

In particular, the propellant-driven metered-dose inhalers release the aerosol cloud at the very high velocity caused by the pressure of the propellant. The open-mouth technique of inhalation [79] helps to slow down the droplets (and to evaporate the volatile excipients). An even more effective solution is to use spacer devices [4,79-87], in which the aerosol cloud can slowed down, the volatile constituents can evaporate, and any large particles will sediment out. Moreover, the patient can then inhale the remaining aerosol under optimal conditions for pulmonary delivery [4,8,56,79], that is, with a slow inspiratory flow rate. 

Many drugs have been formnlated for use with pressurized metered-dose inhalers (pMDIs) (Table 1). The main market for these devices is in the treatment of asthma, allergic diseases, and chronic obstructive pulmonary disease (COPD), for which approximately 500 million pMDIs are produced each year. Their major selling points are that they are cheap and portable. Despite their huge sales, there is increasing concern that the dose of drug patients with asthma receive will vary considerably due to their inhalational technique and to a lesser extent to the variabihty of dose delivery from the pMDI. It is likely, however, that the popularity of pMDIs will continue due to various modifications and additions that are aimed to help with inhalational technique and improve drug delivery. Examples of these include breath-actuated devices, discussed in this chapter, and spacer devices discussed in a subsequent chapter. 

Berg E. In vitro properties of pressurized metered dose inhalers with and without spacer devices. J Aerosol Med 1995 8(suppl 3) 3—11. 

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