Knowing a little of the science that makes something work can really deepen your respect for an every day object.
At the end of 2010 I had the privilege of attending Drug Delivery to the Lungs 21, an event that showcases research in the field of inhaled drug delivery. While many value their inhalers simply for the instant and welcome relief they provide, those of us lucky enough to peer into the world of inhaler research can find powder engineering to really marvel at.
Today’s post continues the series on why particle size is important with the fascinating example of dry powder inhalers (DPIs).
100 square meters
Estimates of the surface area that the lung provides for absorption vary around the 100 square meters figure – a big number. This is, of course, a principal attraction of the pulmonary route for drug delivery – a massive surface area for rapid absorption into the bloodstream.
However, our lungs are guarded by an extremely efficient filtration system. Particles any larger than around five to ten microns are filtered out for ingestion.
DPI developers use the term fine particle dose (FPD) as an in vitro measure of drug delivery efficiency, typically defining it as the amount of material in the sub-5-micron range delivered by the inhaler. A higher FPD means that more of the dose will make it through the lung’s filtration system to the intended target.
The DPI conundrum
The problem with particles this fine is that they can be truly horrible to handle. Inter-particle forces rise steeply as particle size drops below 10 microns so you tend to find the most cohesive materials in this size range. We’re talking about dealing with, and dispersing, individual flour particles here, rather than grains of sand.
To enable DPI manufacture formulators may attach the active to a larger carrier particle making the formulation much easier to handle. However, during use, the energy supplied by the inhaling patient has to be sufficient to strip the active from the carrier, otherwise the user won’t benefit from the drug.
Alternative strategies include engineering the surface of the active ingredient itself to give desirable flow and dispersion properties. This too is no mean feat.
Tools of the trade
We’re happy to be able to provide some tools that give useful data for inhaler development – not just size information, but images of shape and chemical identification too. At the next big gathering of the inhalation community – RDD 2011, in Berlin in May we’ll be conducting a workshop with Nextbreath LLC, showing how, for example, laser diffraction and imaging work supports the extension of dry powder technology to nasal drug delivery.
If you have any insight or information to share on this whole topic please feel free to use the comment section below.