Metered dose inhalers, pressurized vapor pressure

Baeckstroem K, Nilsson PG. Measurements of droplet size distributions from metered dose inhalers with different vapor pressures and contents of surfactant. J Aerosol Sci 1988 19(7) 1097-1100. 

Tzou TZ. Density, excess molar volume, and vapor pressure of propellant mixtures in metered-dose inhalers deviation from ideal mixtures. Respir Drug Delivery YI, Int Symp 1998 439-443. 

Smyth HDC, Mejia-Millan EA, Hickey AJ. The effect of ethanol on solvency vapor pressure, and emitted droplet size of solution metered dose inhalers containing HFA 134a. Respir Drug Delivery VIII 2002 2 735-738. 

Harnor, K. J., Perkins, A. C., Wastie, M., et al. (1993), Effect of vapor pressure on the deposition pattern from solution phase metered dose inhalers, Int. J. Pharm., 95, 111-116. 

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. 

Tetrafluoroethane is a hydrofluorocarbon (HFC) or hydro-fluoroalkane (HFA) aerosol propellant (contains hydrogen, fluorine, and carbon) as contrasted to a CFC (chlorine, fluorine, and carbon). The lack of chlorine in the molecule and the presence of hydrogen reduces the ozone depletion activity to practically zero. Hence tetrafluoroethane can be considered as an alternative to CFCs in the formulation of metered-dose inhalers (MDIs). It has replaced CFC-12 as a refrigerant since it has essentially the same vapor pressure. Its very low Kauri-butanol value and solubility parameter indicate that it is not a good solvent for the commonly used surfactants for MDIs. Sorbitan trioleate, sorbitan sesquioleate, oleic acid, and soya lecithin show limited solubility in tetrafluoroethane and the amount of surfactant that actually dissolves may not be sufficient to keep a drug readily dispersed. 

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