Breathing easier – meeting the challenges in inhaler design
Anyone who knows me will tell you that I am never happier than when standing in front of an audience, sharing my interest in the different applications I get involved in at Malvern. So, I was extremely pleased to be invited to speak at the dry powder inhalers workshop which preceded the recent Management Forum conference on Inhaled Drug Delivery, held in London.
The science of inhaler development has fascinated me, ever since I first attended the Drug Delivery to the Lungs conference 10 years ago. This is partly because the challenge of dispersing powders to a very fine, respirable particle size has been an interest since I did my own research studies at university; and partly because, as a needle-phobic, I look forward to the day when actives such as vaccines can be delivered using inhalation devices rather than injections!
‘Developing dry powder inhalers – experiences and challenges’ attracted a dedicated crowd, and, making my contribution on the use of laser based technologies in formulation screening, I felt privileged to be part of a line-up of exemplary speakers from both industry and academia.
Bioequivalence studies, along with the requirement for developing realistic in vivo-in vitro correlations, were major themes within the conference. The various methods which exist to characterize DPIs were discussed, following the formulation from development through to final use, including the application of imaging methods to determine the site of deposition of an aerosol within the respiratory tract. Examples were given of how QdD approaches have been used to aid the development of robust products. Within this, Jag Shur’s talk on the using of Atomic Force Microscopy to understand the balance of forces which exist with DPI powder blends grabbed my interest. Based on research carried out within Rob Price’s group at Bath University, his presentation showed how an understanding of powder surface properties, and the impact these have on API-excipient particle interactions, can aid formulation development. Took me back to my days as a colloid scientist!
DPI development challenges
I think it’s fair to say that DPI development is technically challenging, and along the way to producing an effective product, there is a need for detailed study of the dynamics of powder entrainment and dispersion, as well as an understanding of the structure of the delivered particles. In my talk I discussed how techniques which can follow the process of particle dispersion, and then identify which species have been dispersed to a respirable particle size, can offer significant benefits, especially when developing new combination therapies.
Laser diffraction for inhaler design
Malvern’s Spraytec really comes into its own here, since laser diffraction particle size analysis, provides a high throughput screening tool to support such studies. By measuring the particle size and concentration of the spray cloud produced by an inhaler in real time, Spraytec allows detailed investigation of aerosolization behavior. This, in turn, enables rapid assessment of how air flow rate or breathing profile affects dispersion.
Image analysis for inhaler design
Further insight comes from considering the structure of the delivered particles. Using automated image analysis systems, such as Malvern’s Morphologi G3, researchers can look at the size and shape of the particles both before and after dispersion. More specifically, image analysis combined with Raman Spectroscopy – for species identification – delivers the detailed information needed to understand how drug particles and excipients interact within any agglomerates that are present. So, a powerful tool for optimising formulations to ensure dispersion of the active(s) to a respirable particle size.
If you visit www.malvern.com/spraytec_oindp you can take a look at some recent articles and application notes which illustrate the way Malvern systems are being used to support the development of inhaled drugs.