Aerosol deposition and emission from a United States Pharmacopeia-induction port when using a pressurized metered-dose inhaler with and without a valved holding chamber

Abstract

The testing of pharmaceutical aerosols includes measuring the aerodynamic particle size distribution, which is usually performed on cascade impactors. In the next generation impactor (NGI), the aerosol dose is introduced through an induction port (IP), being separated into different aerodynamic diameter ranges by seven stages and a micro-orifice collector. The IP plays an important role in estimating the oropharyngeal deposition fraction. While the IP retains mainly large particles, it also tends to retain particles in the respirable range. In this work, the deposition of particles in the IP of an NGI is studied, both experimentally and through computational fluid dynamic (CFD) simulations. Experimental tests are conducted both with the pressurized metered-dose inhaler (pMDI) alone and in conjunction with a cylindrical valved holding chamber (VHC). For each case, the total mass deposition that occurs in the VHC, IP, and NGI stages is measured, as well as the mass median aerodynamic diameter of the aerosol leaving the IP. The CFD simulations show minimal variations in results regardless of the injection method due to the relatively low velocity and spray angle of the pMDI-generated aerosol. If the flap-valve is removed from the VHC, significant particle deposition occurs upstream or within the valve region, with downstream air recirculation contributing to small particle deposition. Based on the CFD results, a correlation is proposed to accurately predict the particle escape fraction of the IP and VHC, which allows estimation of the tannin distribution of particles collected in the NGI stages, especially those corresponding to the range of respirable particles.