Druplet is almost ready...

Warren and I have spent quite a few head-scratching evenings on this one - and most of it is now on my dining table. At least, the components are.

To optimise our αeolus dry powder inhaler core technology we need to properly get to grips with the fundamental physics of the deagglomeration and aerosolisation of the powder formulation. By "properly", I mean in a highly controlled and scientific manner - albeit empirically.

To achieve this we need to go back to first principles, and temporarily forget the requirements of the eventual inhaler product (quite a difficult thing to do, when you've been working on them for so long ??). The questions we seek to answer are:

1. How does the level of kinetic power affect deagglomeration? And,
2. How does the type of kinetic power affect deagglomeration.

The first question is relatively straightforward to test - it has been done many times before, and the answer is typically, "Strongly!" We are developing a technology that defies this rule - after all, having an inhaler whose performance is directly affected by how hard the patient inhales is far from ideal, and indeed one of the primary causes of failure in the clinic - and the reason why so many DPIs under development never make it to market. If we can create a core inhaler technology that achieves consistently high levels of deagglomeration, aerosolisation and ultimately the fine particle dose, and is not influenced by the level of kinetic power, that's a good thing. We want the powder to think that it's an athletic swimmer using the inhaler - even when it's actually a COPD patient with seriously impaired lung function.

The second question is much more tricky to answer, especially in terms of fluidics and aerosol science. A simpler analogy would be as follows...

If your task was to break up a pile of large rocks down to the size of pebbles, and you only had half a day to do it - given the choice, what size of hammer would you use?

The most obvious answer is probably, "The biggest hammer available". Whilst it's true that a huge hammer will almost certainly be capable of smashing the rocks, this is only possible if the user is strong and capable enough to use it. And even if they are - is it the best and most efficient use of their energy? Wielding a huge hammer would be a lot of hard work!

What about choosing the smallest hammer? This sounds like a lot less effort, but perhaps no one would be able to swing it with sufficient speed to break the rock in the first place.

The answer is that there is likely to be an optimal hammer size (or mass) that is just large enough to break the rocks, but requires the lowest input energy to do so, therefore the user tires less quickly and is able to complete the task as efficiently as possible, whilst expending minimal energy. I presented this concept at an inhaler conference in London in 2017 - here's a link to the slow-motion videos I used to demonstrate that a pin hammer is much more effective at cracking nuts than a sledgehammer, for a given energy budget - i.e. the pin hammer and the sledgehammer have equal kinetic energy at the moment of impact...

We have designed the Druplet test rig to enable us to explore the effective size of the hammer, in terms of fluidics, on the performance of our αeolus deagglomeration technology. As passive DPIs are solely reliant upon harnessing a portion of the kinetic power available from the patient's inhalation, understanding how best to deploy this within the inhaler could make the difference between a pass and a fail in the clinic, and ultimately the chance of success for the product.

A sectioned rendering of Druplet - the "magic" happens in the pixelated regions ??

The Druplet test rig will be ready by 2021, and has been designed with as much flexibility and future-proofing as possible. We will be able to test carrier-based formulation as well as API-only, with fill masses from ~5 mg to ~300 mg. This exploratory test rig will enable us to determine the effectiveness of the αeolus DPI technology with any dry powder formulation, across a broad range of inspiratory effort, and characterise the sweet spot in the design space to deliver your formulation optimally.

The Druplet test rig shown connected to a Next Generation Impactor, ready for in vitro testing.

Our plan is to spend 2021 building a deep understanding of the fundamental physics behind our concept, testing a wide range of formulations, and evolving a comprehensive map of the design space. The next generation test rig will be a fully integrated design, that brings in the other primary functions of the αeolus technology. This fully integrated test rig is expected to be ready mid-2021. During 2022 we plan to design and build clinical prototype DPIs that incorporate the optimised αeolus technology, and with Design Verification Testing conducted during early 2023 we will be looking to run clinical studies in that same year.

It is our hope that αeolus will be made available for licensing into a broad range of DPI products - from single-use emergency inhalers, through to convenient multi unit-dose designs, with identical performance across all implementations.

Industrial Designs of DPIs built around the αeolus technology - single use; reusable and multi unit-dose.

2021 is going to be a very exciting year for us, so if you are interested in learning more please get in touch via our website - Cambridge Healthcare Innovations

"You must learn to fly before you can soar with eagles..."