Summary
Leakage from a pressurised metered dose inhaler (pMDI) comes from two sources: the valve-to-canister crimp region and the metering valve’s stem-diaphragm interface. Both regions of the pMDI typically use elastomeric components to create an effective seal. Whilst the valve-to-can crimp is a static seal the stem-diaphragm interface is dynamic, in that the stem slides through the diaphragm each time the pMDI is actuated.
Initial evaluation of propellants 152a and 1234ze on pressure fill metering valves designed for use on propellants 134a and 227 has shown a much-increased leakage rate, especially so with propellant 152a. In the study summarised below, an evaluation of the effect of elastomer material on stem-diaphragm leakage has been performed using placebo formulations comprising propellant 152a with and without ethanol. Three types of elastomer materials have been evaluated: nitrile, EPDM and chlorobutyl under two temperature regimes. Weight loss was determined by weighing units on an analytical balance initially and then again after increasing time periods (in a temperature-controlled environment) ranging from 7 days to 6 months. An annual leakage rate was calculated by linear extrapolation.
Results indicate a clear difference in stem-diaphragm leakage dependent on the type of elastomer used to manufacture the diaphragm component; in the worst-case scenario of a 40°C storage regime and units filled with propellant 152a and 10% (w/w) ethanol, maximum leakage from a pMDI with a chlorobutyl diaphragm was 56 mg/year, compared to 225 mg/year with an EPDM diaphragm and 1076 mg/year with a nitrile diaphragm.