Validating AIM-Based Instrumentation and Associated Measurement Techniques - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 304

Table 10.10 pMDI products evaluated by Guo et al . with the FPD-AVCI [ 33 ]

Formulation
type Product name API Propellant Excipients

Aerobid ® Flunisolide CFC Sorbitan

trioleate

Suspension

Combivent ® Salbutamol (AS)/ipratropium

bromide (IB)

CFC Soya lecithin Suspension

MaxAir™ Pirbuterol CFC Sorbitan

trioleate

Suspension

Advair ® Fluticasone propionate (FP)/

salmeterol xinafoate (SX)

HFA None Suspension

Flovent-110 ® Fluticasone propionate HFA None Suspension

Proair ® Salbutamol HFA Ethanol Suspension

Proventil™ Salbutamol HFA Oleic acid,

ethanol

Suspension

Atrovent ® Ipratropium bromide HFA Water, citric

acid, ethanol

Solution

This pattern of divergence between the various abbreviated options was comparable
in absolute terms with the behavior observed with measures of FPM <4.7μm . The fact that
the addition of Brij-coated filters to the collection dishes of the FPD-AVCI only
slightly reduced EPM <1.1μm suggests that particle re-entrainment is an unlikely cause.
However, it should be emphasized that these differences between the abbreviated
systems with or without surfactant-saturated filters to control particle bounce and
re-entrainment and the control ACI were small, and therefore unlikely to prevent
any of these options being used as an abbreviated impactor of choice with this par-
ticular formulation. This type of detailed study illustrates well the approach that
should be taken when validating a potential AIM-based system for any OIP.
Guo et al . have also recently presented measurements undertaken with the
Westech FPD-AVCI impactor, evaluating eight different suspension and solution
pMDIs (Table 10.10 ) [ 33 ]. CPF >5.0μm , FPF <5.0μm , and EPF <1.0μm determined by the
FPD-AVCI were compared to the same metrics obtained by means of an 8-stage
nonviable ACI. Ten actuations from the pMDI-on-test were delivered into the FPD-
AVCI or ACI, and API recovery proceeded afterward by validated quantitative
chemical analysis. Since the ACI does not have stages with cut-off diameters pre-
cisely at 5 m, the three measures of interest were interpolated from the

cumulative APSD data obtained with the full-resolution CI.
Equivalent total API recovery was observed for all pMDI products between FPD
and ACI (Fig. 10.26 ). Although agreement between FPD-AVCI and ACI data was
generally good, Guo et al . found small but significant differences in all three
subfractions with some of the formulations, especially with CPF >5.0μm , with the val-
ues obtained using the FPD-AVCI higher than their ACI-determined counterparts
(Fig. 10.27 ).
Guo et al. concluded that, whether or not the pMDI is a solution or suspension,
formulation was not the only deciding factor on whether or not there is a divergence
between abbreviated and full-resolution data [ 33 ].

μ m and 1 μ