Design and pharmaceutical applications of a low-flow-rate single-nozzle impactor.

A new low-flow-rate (0.5L/min) single-nozzle impactor for the concentration of dilute aerosol particles with selected pharmaceutical applications is described in this paper. The impactor can be configured up to 11 stages with a wide range of cutoff diameters from 0.6μm to 21.1μm, enabling convenient sampling of inhalable drug particles from inhalation devices and drug production processes. Its unique single-nozzle design and removable impaction plate allow direct sample transfer for subsequent compositional, morphological, solid-state, and other analysis. Agreement between the measured size distribution of fluticasone propionate particles actuated from commercial pMDI Flixotide® 250 Evohaler® and reported data in the literature verified that the impactor stages have accurate cutoff diameters as designed. The multi-stage configuration of the impactor allows rapid separation of polydisperse aerosol particles into different size classes for further characterization. Overlapping of the Raman spectra of the double-component powders from the Seretide® 250 pMDI collected using two different methods demonstrated the applicability of the impactor for a representative sampling of multi-component aerosol particles for bulk composition analysis. A time-dependent and size-dependent stability study was conducted consuming only a single sample canister with 80mg of amorphous indomethacin particles suspended in HFA-134a. It was found that amorphous indomethacin particles converted to the γ crystalline polymorph upon storage at 45°C and that the crystallization rate is strongly size dependent. With its highly effective aerosol collection capability and accurate cutoff diameters for aerosol classification, the impactor will have various applications in the pharmaceutical industry.