The critical imperative of sustainability emerged as a hot and emotive topic at last year’s Drug Delivery to the Lungs (DDL) conference – and once again it took centre stage as online attendees gathered for the DDL2020 Christmas Lectures last week. This pressing issue is also the natural starting point here, as I share my thoughts, insights and reflections on the event highlights. As the story unfolds, please forgive my clear bias: I am significantly more partial to the fundamental physics of drug delivery devices than to therapeutic formulation strategies.
Patient-first sustainable solutions
With our industry wrestling with its position on balancing environmental impact, effective patient treatment and product cost, a number of delegates took the opportunity to advance the debate. A highlight was the open discussion hosted by Michelle Dawson (Pharmaron UK) and Josué Sznitman (Israel Institute of Technology). The lively conversation resolved with agreement that the patient’s needs must remain at the heart of any initiative to push for more sustainable solutions.
Further, it was clear that sustainability needs to be driven across the complete lifecycle of devices – including formulation – with praise given for the recent progress made. However, this comes with trade-offs. For instance, refillable devices can lead to significant carbon footprint reduction (70% reduction for the latest refillable Respimat), but care is needed to manage changes to the user burden.
The use of sustainable polymers also brings exciting opportunities in the medical industry, as long as their functional and mechanical properties are carefully considered during the development. The audience additionally raised the dilemma of balancing connectivity and sustainability, with the use of electronic components conflicting with the general sustainability effort. This reinforces the need for connectivity in inhalers to be considered and justified carefully.
The broader considerations for a sustainable future are discussed in the unmissable and captivating video of my friend and colleague Dan Cowen. He described the path to a sustainable future for inhalation products, where sustainability is considered in a product lifecycle, whilst not necessarily coming with a compromise. Dan expertly lays out the contextual background, providing a list of considerations and potential actions for product development that will bring an enduring and substantial positive difference to this effort.
Harish Jeswani (University of Manchester) provided an analysis of the environmental impact of inhalers through a comparison of factors between MDIs and DPIs, where the dominance of propellant was unequivocal. Beyond this, his work pointed out the potential relative benefits of strategies for the recycling and reduction of propellant usage, rather than pushing to shift the industry towards DPIs.
Additionally, Beate Treffler (Avient Corporation) provided key insights into the possibilities for bio-based medical grade materials. She showcased some emerging potential, with a proviso that there remains a long way to go before realistic options are available and adopted by designers.
On broader reflection, it is interesting to consider a future where disease management is less common in the advent of curative cell and gene therapies, particularly for non-communicable diseases. Reducing the needs for chronic maintenance devices will undoubtedly have a positive sustainability impact, though bioengineering is still scrambling to get there. Nevertheless, the developing signs are strong – and our bioengineering team has certainly had a busy year.
The limitations of pMDIs and DPIs
David Harris (Cambridge Healthcare Innovations) and Lea Ann Dailey (University of Vienna) hosted a compelling discussion on the balances and differences between pressurised metered dose inhalers (pMDIs) and dry powder inhalers (DPIs). Despite their long history in respiratory therapy, these devices have a remarkable number of known issues, which Sinthia Bosnic-Anticevich (University of Sydney) covered in her talk.
Variations in user interactions with devices was highlighted as a particular concern. For instance, how is a patient to know the breathing effort required for a given device, as these diverge greatly between pMDIs and DPIs, and even across different DPIs? It was clear that there has been a significant lack of innovation in this area that truly meets the key stakeholder needs. Interestingly, someone mused that vaping devices, when compared to medical devices, often seem to offer reduced stigma and increased compliance.
The limitations of these devices were examined, alongside considerations for what might be an ‘ideal’ delivery device, as well as the considerable benefits of academic/industrial collaboration in improving the understanding of their underlying physics. For many it was surprising that despite the advent of robust and powerful experimental and computational methods, there remains challenging physics at the heart of these device. Hence the need for continued research in this area. The pressurised metered dose inhaler and the dry powder inhaler were well represented at DDL. Let’s consider each in turn.
Pressurised Metered Dose Inhalers
Building a deeper understanding of pMDIs remains a key area of focus, given their widespread use and the complexity of the underlying physics. I remember the excitement generated by Prior Medical when they presented their phase contrast x-ray imaging of a pMDI at DDL2016. Four years later, Barzin Gavtash (Kindeva Drug Delivery Limited) showed the use of in silico (VOF-CFD) methods for modelling cavitating propellant flow inside a pressurised metered dose inhaler stem and sump. They achieved good qualitative agreement against similar imaging techniques.
Alongside this, Daniel Duke (Monash University) developed an initial computational fluid dynamics approach to model the complex physics of a pMDI spray actuation and generation. It allows insights to be drawn about how new actuator/sump geometries would perform (such as, a twin orifice geometry), in terms of plume characteristics, and to begin to unpick the driving spray physics.
Though experimentally or computationally challenging, it will be interesting to see the link developed between the complex dynamics within the pMDI device and the resultant key performance attributes of the generated aerosol plume.
Dry Powder Inhalers
Similar to its counterpart, there were many scientific investigations and probing discussions around the performance and physics of DPIs. Vishal Chaugule (Monash University) outlined an approach on the assessment of DPIs that combined computational (CFD) and experimental (PIV and impaction) methods to provide insights to deagglomeration in different DPI configurations. Here the complementary methods provided good correlation and delivered additional insight into the processes for aerosol dispersion and aerosol deposition.
Milica Stankovic-Brandl (Research Center Pharmaceutical Engineering) engaged us with an overview of work focused on understanding the importance of pierced capsule opening areas, and resultant airflow through the capsule, on capsule inhaler performance. Comparative experiment and computation simulations were performed on capsule openings. Interestingly, lubricating capsules reduces the pierced opening areas, though fine particle dose remains similar.
Kai Berkenfeld (University of Bonn) presented research on the impact of layer height in rapid prototyping on the usefulness of prototypes for performance evaluation. Despite relatively large variations in certain key areas of the geometry, the insights were still consistent and good guiding data was achieved even with coarse models.
It was pleasing to hear Adithya Gurumurthy (North Carolina State University), who demonstrated the potential for enhancing lung delivery via the use of a helical/swirl flow at the exit of the delivery device. This was based on the use of in-silico simulations that capture the balance of competing deposition mechanisms (inertia, sedimentation and diffusion) against swirl strength and inhalation effort.
Widening the spotlight
There were two other presentations that really caught my attention. Firstly, Josué Sznitman (Israel Institute of Technology), presented a range of experimental and ex-vivo data to support using surfactant foams for treatment of COVID-19 patients with ARDS. The mechanism of operation is based around reducing gravitational influence, by using foam for instilled treatments to achieve increased lung dispersion. There is evidence that surfactant replacement therapy can improve outcomes for such patients, though there may be broader benefits to such an approach in the delivery of other treatments.
Secondly, Anders Broo (AstraZeneca), provided a balanced view on using artificial intelligence to increase value across the pharma R&D chain, alongside his thoughts on a future for smart labs. Anders presented an example of using AI for screening new formulations, where it excels at image-based classification. I couldn’t have agreed more with Anders. Given their value, such intelligent machines are here to stay, and we need to learn to work with them to maximise that benefit.
Overall, I feel the conference format worked really well, with depth and discussion in key areas, as well as providing a broad range of on-demand topics to meet the diverse interests of attendees. It was great to see DDL acknowledge Dr Jenny Lam, who received the Emerging Scientist Award for her work applying spray drying and freezing techniques to dry powder therapeutic molecules, for oral and nasal inhalation.
From my perspective, it was a very different experience patrolling the booth and engaging with passers-by this year. The loss of eye-contact and tactile greetings were keenly felt, but engaging conversations were virtually achieved. If you missed it, you can catch up via the conference website for a limited time. And if you have thoughts to share or questions to ask, please feel free to reach out.
