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Metered-dose inhaler formulation of fluticasone-17-propionate micronized with supercritical carbon dioxide using the alternative propellant HFA-227

1998; Elsevier BV; Volume: 173; Issue: 1-2 Linguagem: Inglês

10.1016/s0378-5173(98)00237-3

1873-3476

Hartwig Steckel, Bernd W. Müller,

nanoparticles nucleation surface interactions

The commonly used propellants from the chlorofluorocarbon (CFC) type are known to deplete the ozone layer so that replacement by alternative propellants is required. The aim of this study was to show the feasibility to reformulate fluticasone-17-propionate, a very promising anti-inflammatory drug, using the propellant heptafluoropropane (HFA-227). The glucocorticoid was micronized by a new technique using supercritical carbon dioxide (aerosol solvent extraction system, ASES) resulting in very fine particles. Metered-dose inhaler formulations were performed using a pressure filling technique. ASES products showed a very narrow particle size distribution with slightly different crystal properties. These products were compared to metered-dose inhaler formulations with jet milled drug, the marketed Flutide™ MDI and the Flutide™ Diskus™ powder inhaler. The fine particle fractions, determined with a twin stage impinger, of CFC-free formulations with one ASES product were equivalent to the CFC-formulation Flutide™ both having a fine particle fraction of roughly 60%. A variation of actuator orifice diameter even increased the fraction of drug particles <6.4 μm. The study proved the feasibility of reformulating fluticasone propionate with the alternative propellant HFA-227. The processing of steroids using supercritical carbon dioxide proved to be a useful technique for the micronization and surface coating with a surfactant in one process step.