Cascade Impactor Performance of Commercial pMDI Formulations Using Modified Induction Ports.

The induction port (IP) for aerosol analysis with the Next Generation Pharmaceutical Impactor as monographed in the United States and European pharmacopoeia (USPIP) lacks physiological relevance, which, amongst other reasons, has been identified as critical for the predictability of in vitro aerosol data to lung deposition observed in vivo. In this publication, we report the impact of replacing the USPIP with two modified induction ports, which were designed based around geometries derived from a computer tomographic scan of a human trachea and the distal section of the USPIP. Test formulations were selected on the basis of availability of in vivo lung deposition data so that results obtained in vitro could be evaluated for their predictability. All formulations assessed showed increased deposition in the modified induction ports, and different mechanisms of particle deposition have been identified. In vitro predictions of the lung deposition were found to correlate well with the in vivo observations reported using the modified induction ports. Furthermore, the quality of the correlation was found superior to the one achieved with the USPIP with an average deviation of the predicted from observed values (n = 10) of 6 ± 4, 12 ± 6, and 16 ± 6% for the modified induction ports (mIP and mIPext) and the USPIP, respectively, when using a fine particle fraction (FPF) cutoff value of 5 μm. Using a FPF cutoff value of 3 μm yielded a more accurate in vitro-in vivo correlation with an average deviation of the predicted from observed values of 5 ± 4, 7 ± 5, and 8 ± 4% for the mIP, mIPext, and USPIP, respectively. For both FPF size cutoff values, the mIP yielded the most accurate in vitro-in vivo correlation.