Asthma pressurised metered dose inhaler performance: propellant effect studies in delivery systems

Abstract

Background: Current pressurised metered dose asthma inhaler (pMDI) propellants are not inert pharmacologically as were previous chlorofluorocarbons, have smooth muscle relaxant‚ partial pressure effects in the lungs and inhaled hydrofluoroalkane 134a (norflurane) has anaesthetic effects. Volumes of propellant gas per actuation have never been measured. Methods:In-vitro studies measured gas volumes produced by pMDIs on air oxygen (O 2 ) levels in valved holding chambers (VHC) and the falls in O 2 % following actuation into lung ventilator delivery devices.Results: Volumes of propellant gas hydrofluoroalkane (HFA) 134a and 227ea and redundant chlorofluorocarbons (CFC) varied from 7 ml per actuation from a small salbutamol HFA inhaler to 16 ml from the larger. Similar-sized CFC pMDI volumes were 15.6 and 20.4 ml. Each HFA salbutamol inhaler has 220 full volume discharges; total volume of gas from a small 134a pMDI was 1640 ml, and large 3885 ml. Sensing the presence of liquid propellant by shaking was felt at the 220th discharge in both large and small inhalers. Because of a partial pressure effect, VHC O 2 % in air was reduced to 11% in the smallest 127 ml volume VHC following 10 actuations of a large 134a salbutamol inhaler. The four ventilator delivery devices studied lowered 100% oxygen levels to a range of 93 to 81% after five actuations, depending on the device and type of pMDI used. Conclusion:Pressurised inhaler propellants require further study to assess smooth muscle relaxing properties.

Costs of switching to low global warming potential inhalers. An economic and carbon footprint analysis of NHS prescription data in England

“…All salbutamol MDIs use HFA134a, with a GWP of 1300. There are two types of salbutamol MDIs, one a small volume MDI containing alcohol as a co-solvent, which requires less HFA propellant than the large volume alcohol-free type 20. A study comparing a large volume inhaler Ventolin Evohaler with small volume Salamol inhaler found the weight of the contents (mainly HFA134a propellant) to be 17.32 and 7.88 g, respectively.…”

Understanding Dry Powder Inhalers: Key Technical and Patient Preference Attributes

“…In response to these changes, the pharmaceutical industry increased its focus on the development of dry powder inhalers [4]. While pressurised MDIs (pMDIs) remain the most commonly prescribed type of inhaler [5], even in the post-CFC era, they still pose an environmental hazard [6], as the modern propellants (hydrofluorocarbons and hydrofluoroalkanes) are roughly 1300 times more potent than CO 2 as greenhouse gases. In fact, the carbon footprint of pMDIs has been reported to be over 100-fold greater than that of DPIs [7].…”

Paradoxical Bronchoconstriction with Short-Acting Beta Agonist

“…We further considered that 1,1,1,2-tetrafluoroethane, also known as HFA-134a, the propellant used in all 3 aerosolized formulations and his fluticasone/salmeterol formulation, might be a cause of the bronchospasm. We considered the propellant to be a less likely cause of the patient’s symptoms given that hydrofluoroalkanes are potent smooth-muscle relaxants with effects demonstrated on bronchi [ 19 ] and there was absence of decreased pulmonary function with use of all inhalers utilizing HFA-134a as the propellant. We specifically would have expected our ipratropium inhaler (which contains similar excipients as the SABA formulations) to cause a decrease in pulmonary function; however, this was not observed in our testing.…”