Inhaler propellants

Smith, D.L., S.L.Aikman, L.J.Coulby, J.Sutcliffe, and BJ.O Conner. 1994. The attenuation of methacholine-induced bronchoconstriction by salmeterol comparison between an alternative metered dose inhaler propellant GR106642X and chlorofluorocarbons 11 and 12. Eur. Resp. J. 7 (Suppl. 18) 318s. 

Taggart, S.C.O., A.Custovic, D.H.Richards, and A.Woodcock 1994. An alternative metered dose inhaler propellant GR106642X comparison to chlorofluorocarbon 11 and 12 in the attenuation of histamine-induced bronchoconstriction by salbutamol. Eur. Resp. J. (Suppl. 18) 400s. 

Prior to 1985, chlorofluorocarbons were widely used as inert nontoxic inhaler propellants these compounds are now all but banned. Consequently, much recent research has centered on the development of dry powder inhalers, which deliver the active ingredient as ultrafine particles directly to the lungs with minimal deposition in the mouth and trachea. Some of these devices are activated directly by the inspiration of the patient without the need to coordinate activation and inspiration. 

The products are available as tablets, capsules, liquids (in the form of solutions, suspensions, emulsions, gels, or injectables), creams (usually oil-in-water emulsions), ointments (usually water-in-oil emulsions), and aerosols, which contain inhalable products or products suitable for external use. Propellants used in aerosols include chlorofluorocarbons (CFCs), which are being phased out. Recently, butane has been used as a propellant in externally applied products. The major manufactured groups include ... 

Some physicians recommend epinephrine metered-dose inhalers as an alternative to epinephrine autoinjectors. While a few inhalations might relieve mild or moderate respiratory symptoms, for relief of life-threatening airway obstruction or shock, adults need to inhale 20-30 puffs and children need to inhale 10-20 puffs, which is hard to do [35]. Epinephrine metered-dose inhalers contain chlorofluorocarbon propellants. For environmental reasons, they might not be manufactured in the future. 

CFC, chlorofluorocarbon propellant HFA, hydrofluoroalkane propellant MDI, metered-dose inhaler. 

The vapor pressure and density of propellants are employed to assist in formulation. The vapor pressure dictates the force of emission of the droplets from the metering valve of the inhaler. The force of emission is... 

Fig. 4 (A) Propellant-driven metered dose inhaler. (B) Metering valve.

AJ Hickey, RM Evans. Aerosol generation from propellent-driven metered dose inhalers. In AJ Hickey, ed. Inhalation Aerosols. New York Marcel Dekker, Inc., 1996, pp. 417-439. 

A man habitually enjoyed the euphoric effects of inhaling whiffs of nitrous oxide in seclusion, and kept a cylinder of the gas in his sedan for that purpose. He decided to spray the faded car seats with an aerosol can of vinyl dressing (propanc/butanc propellant) with the windows closed. Then he had a whiff of gas from the briefly opened cylinder, and settled back to enjoy the euphoria and a cigarette. He was lucky to survive the resulting explosion of the fuel/oxidant mixture in a closed vessel [2],... 

The AEGL-1 concentration was based on a 1-hour (h) no-effect concentration of 8,000 parts per million (ppm) in healthy human subjects (Emmen et al. 2000). This concentration was without effects on pulmonary function, respiratory parameters, the eyes (irritation), or the cardiovascular system. Because this concentration is considerably below that causing any adverse effect in animal studies, an intraspecies uncertainty factor (UF) of 1 was applied. The intraspecies UF of 1 is supported by the absence of adverse effects in therapy tests with patients with severe chronic obstructive pulmonary disease and adult and pediatric asthmatics who were tested with metered-dose inhalers containing HFC-134a as the propellant. Because blood concentrations in this study approached equilibrium following 55 minutes (min) of exposure and effects are determined by blood concentrations, the value of 8,000 ppm was made equivalent across all time periods. The AEGL-1 of 8,000 ppm is supported by the absence of adverse effects in experimental animals that inhaled considerably higher concentrations. No adverse effects were observed in rats exposed at 81,000 ppm for 4 h (Silber and Kennedy 1979) or in rats exposed... 

Donnell, D., L.I.Harrison, S.Ward, N.M.Klinger, B.P.Ekholm, K.M.Cooper, I. Porietis, and J.McEwen. 1995. Acute safety of the CFC-free propellant HFA134a from a pressurized metered dose inhaler. Eur. J. Clin. Pharmacol. 48 473— 477. ... 

Intraspecies 1—this no-effect concentration for eight healthy individuals was far below concentrations causing effects in animals. At this low exposure concentration there was no indication of differences in sensitivity among the subjects. This uncertainty factor is supported by the lack of effects in COPD and adult and pediatric asthmatic patients treated with metered-dose inhalers containing HFC-134a as a propellant. 

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