To See an animated video of our patented technology (A3G - Automated Andersen Cascade Impactor) click on image to the right side
There are several impactors available on the market for measuring particle size distribution from inhaled drugs or an air sample.
"Andersen Cascade Impactor or ACI, has been the impactor of choice, and to date almost all of the particle size distribution data submitted to the FDA has been obtained using the ACI. Particle sizes in the 1 to 5 micron range penetrate get deep into the lungs, permitting ready absorption of the drug into the blood, and thus are most efficacious. For this reason the US FDA and other regulatory agencies throughout the world requires extensive particle size distribution data from the drug companies".
However the ACI greatly suffers from low productivity, typically two to four dose determinations per day and from operator induced data variability. At about two dose determinations per day, doing the test manually, it takes years to generate the data and get regulatory approval from the FDA.
The Next Generation Impactor or the NGI was invented to overcome the low productivity issues experienced by the Andersen Cascade Impactor. Traditionally it was thought that the ACI is impossible to automate. Many companies have switched to the NGI and as more and more people have begun using it, they too have experienced issues with it this then is not the answer that most people thought it would be. Typically users can get four to ten dose determinations per day per operator.
The "A3G" is a third generation impactor that has all the advantages of the first and second generation impactors (the ACI and NGI) with none of the disadvantages of either technology.
| |
A3G |
NGI
|
| Productivity |
40 Dose Determinations per day |
Four to ten Dose determinations per day per operator |
| Flight path of the aerosol particles |
Same as in the ACI |
At least twice as long as in the ACI. To prevent aerosol droplet evaporation, many people have started to freeze their NGIs prior to use, thus severely restricting throughput and increasing cost. Without the freezing step, the data is biased more towards the fine particle fraction. |
| Mass Balance |
>98% Mass Balance is obtained, same as manual Andersen Cascade Impactor. All parts get cleaned between each experiment |
Much poorer mass balance then the ACI as powder drug accumulates in the passageways integrated into the body of the NGI, which are difficult to clean. Without periodic cleaning the accumulated drug in the passageways will spike release with the flow onto the collection cups, causing data spikes and crossovers between experiments. Again this limits the actual productivity obtained with the NGI. |
| Impactor Plate/cup handling |
No handling of any plates/cups |
Requires manual cup handling for sample processing, increases chances of analyst error, and limiting throughput |
| Plate/cup Saturation |
Particles are distributed evenly over greater surface area than NGI (more surface area, better adhesion of particles) |
NGI has fewer jets per stage therefore concentrating impacting particles on a smaller surface area. |
| Air Flow |
Up to 90 liters per minute with minus stages |
Up to 100 liters per minute |
| Plate Coating for DPIs |
No coating required |
Requires that cups/plates be coated |
The ACI consists of a cascade of discs stacked, one on top of each other and sealed from the environment, as shown in the picture on the left.
The picture on left shows the Next Generation Impactor. To increase productivity the number of individual parts has been reduced considerably. All of the cups shown in the bottom of the picture are integrated into a tray thus the operator has to handle a tray at a time. However the scope for automation is limited to solvent dispensing and sample collection. The washing is still all manual. The air passages are integrated into the body of the impactor (visible as large holes in the picture). They are difficult to clean and lead to drug accumulation and cross-over data errors. Further, the flight path of the aerosol particle is twice as long as in the ACI. This long path leads to droplet evaporation in case of the pMDI, and the errors tend to be biased towards fine particle fraction. To prevent droplet evaporation, scientists have to freeze/cool the NGI prior to use, making its productivity much lower than claimed and the process very expensive.
