Q: What benefits are offered by extrafine particles?
A: There is growing evidence to suggest that finer aerosols may enable us to effectively direct particles into more efficacious areas of the lung and to achieve a more uniform localized response. Furthermore, data we presented at RDD 2016 demonstrate that finer particles could deliver performance that is more independent of the flow rate applied during use, which would reduce the variability associated with different patient groups.
Better performance in either of these areas could deliver substantial gains in clinical efficacy.
Q: Why do you think that extrafine particles would deposit more efficaciously?
A: Since I began my career in this field, around 20 years ago, the main drivers for improvement have been 1) advances in device design, 2) better characterization and knowledge of drug formulations, and 3) an enhanced understanding of human physiology.
Improvements in analytical capabilities across the board have made it easier to understand the interplay between device, formulation, and patient, and how to control performance to meet our aims. We continue to refine our understanding of how to improve upon what are, in general, relatively low levels of drug delivery efficiency.
Understanding where the formulation needs to be deposited in the lung for greatest efficacy, and the particle size needed to achieve this deposition, has always been crucial. Historically we’ve focused on the behavior of particles within the 1-5 µm range, on the premise that particles need to be less than 5 µm to reach the lung, but particles of less than 1 µm tend to be exhaled.
Recent studies suggest that it may be time to re-examine this premise and look more closely at particles towards the lower end of this range, and indeed finer. A review by Usmani, for example, highlighted that persistent small airway dysfunction is a recognized trait in certain asthma sufferers. These studies showed that extrafine particles could, in fact, penetrate deep into the lung thereby “unlocking the small airways compartment.”