Take a deep breath….
Written by: Anne Virden
Things were hectic in Edinburgh last week where, despite the weather, many people made it to the 21st Drug Delivery to the Lungs conference. It was a great place to catch up with what’s happening in pulmonary and nasal drug delivery, with both industry and academia very well represented. This was my first time at DDL, so everything was new to me.
Hot topics at DDL
The first day of the conference highlighted the importance of two key issues for this highly scientific community:
- Understanding how products behave in the body
- Increasing the productivity of inhaled product testing
The initial series of talks were all centred around the first issue. I found the lung imaging work presented by Professor Beth Laube from John Hopkins University fascinating. A very different type of image analysis to the one I’m used to, but compelling for exactly the same reasons. A picture says a thousand words.
More generally, though, the whole first session really reminded me of the scale of the task of inhaled product development. There are all the challenges surrounding efficient drug delivery to the right part of the pulmonary system, which is where we tend to focus our work, but then there is the equally important issue of ensuring controlled and effective uptake of the drug in the body and how this can be accurately measured. Learning to control both seems to be demanding but absorbing, judging by the conversations I had during the conference.
Thursday’s session on advances in formulation and analytical science included a very interesting presentation looking at a different approach to developing carriers to improve the efficiency of dry powder inhalers. By looking at the relationship between particle size and the forces of adhesion. Hugh Smyth from the University of Texas at Austin presented work where large polystyrene beads were used as the carrier. Coating the active onto these large beads increases the detachment forces, delivering a greater fine particle fraction at low flow rates, in what looks like a really clever device.
The desire for greater productivity in testing was very evident here, and the efficient generation of relevant data for both development work and for QC an important goal. The EPAG workshop that kicked off DDL was all about abbreviated impactor measurement, a streamlined version of multistage cascade impactor testing, which is mandatory for all inhaled products. I know from talking to people about the use of laser diffraction in inhaled product testing that cascade impaction, although valued because of the data it provides, can be time-consuming and labour-intensive, so this development could be good news.
Image analysis and laser diffraction
The poster we presented, ‘Characterizing a Nasal Spray Formulation from Droplet to API Particle Size’, focused on using automated image analysis and laser diffraction together to study OINDPs (orally inhaled and nasal drug products). Both of these techniques are fast, automated and easy to use. Together they provide information that supports nasal spray development in line with guidance laid down by the FDA (‘Bioequivalance (BE) and bioavailability (BA) studies for nasal sprays and nasal aerosols for local action’ ).
With laser diffraction you can measure the droplet size of a nasal spray in real-time to assess likely deposition and retention in the nasal passages. You can then use imaging to look at how the spray process impacts the size of the active, a parameter that can influence bioavailability at the site of deposition. Automated imaging is so much easier than manual microscopy because you can measure thousands of particles in just a few minutes, and then classify, to gather data solely for the active rather than any other insolubles present. We described how the capabilities of imaging can be further extended using Raman spectroscopy, enabling precise identification of the state of dispersion of the active and excipients particles.
…and we won a prize!
The use of imaging and Raman spectroscopy together, with the new Morphologi G3-ID system, was viewed as ‘revolutionary’ by the poster judging panel, offering researchers a unique tool for understanding the degree of interaction between APIs and excipients within OINDP formulations. They therefore awarded Deborah Huck, lead author on our paper, the Industry poster award!
Making a contribution
I’ve left DDL having heard fascinating tales from the frontline about the analytical demands of inhaled product development, and with a clear message that the technologies we provide really make a difference. This is an area where imaging and laser diffraction not only complement one another, but also complement the many other techniques applied by inhalation scientists. I’ve also learnt a few things about the history of inhaler technology and its connections to our host city from Mark Sanders’ talk on the history of active or propelled aerosols. Finally, I now know where to go to look at some truly odd looking devices – http://www.inhalatorium.com/.