Both spacers and VHCs introduce a certain amount of “dead” volume that can impact both the drug quantity and the APSD of the emitted dose because larger particles tend to stick to the interior walls of the add-on device due to inertial impaction caused by the high velocity, ballistic nature of the aerosol generation.
In addition, any delay between actuation and inhalation allows time for processes such as enhanced aerosol expansion and co-solvent evaporation, gravitational sedimentation, and electrostatic deposition to take place, potentially affecting the emitted dose.
Q: How do the new testing methods account for use of a spacer/VHC?
A: Patients using a spacer or VHC are normally instructed to breathe tidally instead of using one steady forced inhalation as they would with an MDI alone, so the new methods require use of a breathing simulator to measure ED rather than a constant flow rate vacuum pump. The breathing simulator is capable of replicating the sinusoidal tidal breathing profiles generated by various types of patients, with profiles covering neonate, infant, child and adult patient groups.
The collection apparatus for measuring ED from an MDI with a spacer/VHC also differs slightly from the apparatus for testing MDIs alone, although the dose is collected onto a filter for subsequent chemical analysis in much the same way.
The new method for ED testing of VHCs includes an assessment of the valve mechanism’s efficiency by simulating the best case “fully coordinated” actuation, where the patient inhales exactly at the same time as actuation, as well as the worst-case scenario of “fully un-coordinated” actuation and inhalation, where the patient exhales at precisely the point of MDI actuation. The ratio of ED values under each condition defines the efficiency of the valve.
For measurement of APSD with spacers/VHCs, time delays are introduced between MDI actuation and sampling by the cascade impactor, which by its design is a constant flow rate device and is operated at a flow rate that is broadly appropriate for the patient category. The delays, which are typically 2, 5 or 10 seconds between MDI actuation and the onset of flow, simulate conditions where the patient fails to co-ordinate actuation with inhalation.
