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.