How do particles interact inside powders? It’s a question that research partners Prof. Darragh Murnane and Dr. Parmesh Gajjar must work at nanometer scales to answer. Undeterred by dead ends, they use X-ray microscopy and AI to deliver affordable inhaled therapies and push the limits of their field.
An estimated 262 million people worldwide were affected by asthma in 2019, according to the Global Asthma Report. Pollution and smoking are seen as major drivers for cases that have caused child fatalities over recent years. Yet as Europe and North America see a decline in smoking, developing economies unable to afford ongoing medication have seen an increase in trends. Research partners Dr. Parmesh Gajjar and Prof. Darragh Murnane view this as a fundamental reason for why more generic products are needed on the market. Dr. Gajjar is a Visiting Researcher from the X-ray imaging facility at the University of Manchester and Chief Technology Officer at InformiX Pharma Ltd. Murnane is a Professor of Pharmaceutics at the University of Hertfordshire and Chief Scientific Officer at InformiX Pharma Ltd. For over 20 years, he has researched inhaled therapies and designed easier-to-use devices that make generic products more accessible and affordable.
Their work together on the INFORM Project tries to understand how powders behave: how they are released from aerosols and what factors control the aerosolization. Their goal is to develop effective respiratory products that help aerosols into the lungs to treat these diseases. Also how to match the right device with the right patient so that asthma sufferers know when to take their medication. “When I was growing up, both me and my brother had really bad asthma. You're always subconsciously thinking about your breathing,” says Dr. Gajjar. “It’s a problem with the industrialization of society – there’s a big rise in the number of people with asthma” says Prof. Murnane.
Gaps in the Inhaled Space
Some innovative pharmaceutical companies have responded to these concerning trends by offering new products. However there is a difficult and yet urgent need to develop respiratory products that help aerosols into the lungs to treat these diseases. Until now, it has not been possible to look inside the powders – to understand what their substructures are. “There are other respiratory diseases which are still not targeted” says Prof. Murnane “yet it's so important for how the aerosols behave and how they're generated.” This set the background for their explorations with X-ray microscopy: a technique that provides non-destructive microstructural information of pharmaceutical powder structures. “X-ray computed tomography has not really been used in the inhaled space because it presents a really difficult challenge” says Dr. Gajjar: “we were stepping into the unknown… trying to push the boundaries a little to see.”
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Darragh Murnane, Professor of Pharmaceutics from University of Herfordshire and Dr. Parmesh Gajjar, a Visiting Researcher from the University of Manchester speak about their recent experiences with AI enabled X-ray microscopy and how it drastically enhanced their research in powders and inhaled medication development.
X-ray microscopy helped us to look inside those powders – to see how the particles interact within the inhalers.
Previously, Prof. Murnane says that he would study the powders using scanning electron microscopy – which produced great images, but didn’t tell them anything. Undeterred by the dead ends, Dr. Gajjar says “we always ask: can we go one step further?” “X-ray microscopy helped us to look inside those powders to see how the particles interact within the inhalers” says Prof. Murnane. This was also the point at which they started to work on the INFORM project with their colleagues in Manchester. Through the project, Prof. Murnane and Dr. Gajjar receive invaluable feedback from the pharmaceutical industry, who need to be able to both develop and apply the techniques.
AI has learned how to detect the noise and artefacts. It can therefore give us a valuable signal out, which helps us to make assessments of these powders and drive the pharmaceutical development forward.
Light Years Beyond
When working on carrier particles – and when imaging on nanometer scales – the partners came up against the limits of the technique. “We couldn’t achieve everything we wanted to, yet it was still light years beyond anything we’d done up to that point”, says Prof. Murnane, “I always love working in the gap: between things that I don't quite understand.”
Before AI microscopy, they were unable to generate clear images because they couldn’t process their data. “AI has enabled us to close the gap on different datasets and put multiple things together with a richer understanding” Dr. Gajjar says “People are seeing it’s almost like magic – to generate stuff out of thin air.” The problems are rooted in real data and whilst AI is unable to generate this, Gajjar believes that it has helped them to look at complex samples that wouldn't otherwise have been possible. After all, interdisciplinary research is what propels new, interesting discoveries forward.
It can't just be gut instinct, so to have a push-button analysis that non-experts can use is a key outcome.
A Push-Button Analysis for Non-Experts
They also find the speed of analysis exciting. “It currently takes several hours to analyze these powders using X-ray microscopy” says Prof. Murnane. When paired with robust data sets, AI allows the partners to make faster achievements. “It can't just be gut instinct, so to have a push-button analysis that non-experts can use is a key outcome” says Murnane. “One of the aspects that we're trying to introduce is proper metrology of the formulation to guide the processes” says Murnane. Now, regulators have sped up the process for releasing generic products onto the market. They do so by stating that the generic product has the same structure as an innovative one, for example. “So we need to work with a very systematic approach that can confirm the microstructure – the comparability, or similarity, as it's known – between two different products”, says Murnane. As we clamber for net zero, generic asthma products are essential for those most affected by our changing world.