In response to the Montreal Protocol, a salmeterol (Serevent) metered dose inhaler (MDI) has been developed containing the non-chlorofluorocarbon propellant, hydrofluoroalkane 134a (HFA), to replace the marketed Serevent chlorofluorocarbon (CFC) propellant MDI. This paper details the pharmaceutical assessment of salmeterol HFA MDI and confirms that this product meets the current Committee for Proprietary Medicinal Products regulatory requirements, and is comparable to the CFC MDI in product performance. Criteria investigated included fine particle mass (FPM), dose delivery and uniformity, priming requirements and simulated-use-testing. Dose delivery was unaffected by changing product orientation during storage. The mean dose delivered per actuation ranged from 21.3 to 22.4 microg, and all individual doses were within the +/-25% defined limits of the target ex-actuator dose of 21 microg. The FPM results, defined as the mass of particles between 1.1 and 4.7 microm in diameter (the sum of the mass deposited on stages 3-5 of the Andersen Cascade Impactor), were similar for the HFA and CFC products. The mean FPM values of the two HFA clinical batches were 8.7 and 10.1 microg, covering the values obtained during the development, and the one of the CFC clinical batch was 10.0 microg. Comparability in aerosol characteristics was also demonstrated when the salmeterol HFA inhaler was tested using a large volume spacer (Volumatic).

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