Prediction and Assessment of Flammability Hazards Associated with Metered-Dose Inhalers Containing Flammable Propellants

Abstract

Several potential replacements for chlorofluorocarbons (CFCs) in metered-dose inhalers (MDIs) are flammable. The flammability hazard associated with their use was assessed using a range of MDIs containing 0–100% (w/w) n-butane (flammable) in HFC-134a (nonflammable) fitted with either 25-, 63-, or 100-µl metering valves or continuous valves. In flame projection tests each MDI was fired horizontally into a flame, and the ignited flume length emitted from the MDI was measured. Flame projections of ≥60 cm were produced by all formulations fitted with continuous valves which contained ≥40% (w/w) n-butane in HFC-134a. Using metering valves the maximum flame projection obtained was 30 cm. This was observed with a formulation containing 90% (w/w) n-butane in HFC-134a and a 100-µl valve. For a particular formulation, smaller metering valves produced shorter flame projections. Because many MDIs are used in conjunction with extension devices, the likelihood of accidental propellant vapor ignition was determined in Nebuhaler and Inspirease reservoirs and a Breathancer spacer. Ignition was predictable based on propellant composition, metered volume, number of actuations, and spacer capacity. Calculated n-butane concentrations in excess of the lower flammability limit [LFL; 1.9% (v/v)] but below the upper flammability limit [UFL; 8.5% (v/v)] were usually predictive of flammability following ignition by a glowing nichrome wire mounted inside the extension device. No ignition was predicted or observed following one or two 25-µl actuations of 100% n-butane into large volume Nebuhaler (750 ml) or Inspirease (660 ml) devices. Additionally, several other formulations containing lower proportions of n-butane also remained nonflammable, due to failure to reach the LFL. In the small-volume Breathancer spacer (140 ml), nonflammability was usually due to n-butane exceeding its UFL. In this situation further dilution during respiration could result in a flammable mixture. Using a carefully selected propellant blend, metering volume, and spacer design, environmentally acceptable flammable propellants may have considerable utility in MDIs reformulated without CFCs.