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Paul Thorning Interview

What are the challenges that you and colleagues are addressing?

There are a number of challenges. The first challenge, and the most common one, is that the molecules that pharmaceutical companies produce are often highly insoluble and sometimes unstable. Our technology helps to make it easier for these drugs to be dissolved and to be capable of being turned into medicines. Essentially, we solve problems that relate to either crystallisation of molecules – how they crystallise and how they crystallise in a way that is makes them likely to dissolve and a way that keeps them stable over a prolonged shelf-life – and how we engineer and shape the morphology of a particle to be optimised.

We can also combine a number of components into a single particle so we have a drug with perhaps a taste masking agent and an enhancer that facilitates transport across a membrane. So, we are designing particles with their use as a medicine in mind.

 

Can you take an existing medicine and re-purpose it? You talked about transforming a medicine from being administered in one way to a completely different one.

Yes, the first medicine using this technology platform is one that our original company was working with alongside the pharmaceutical company MAP (now owned by Actavis), where we’ve taken a very old injectable product for migraine and, using our technology, have repurposed it as an inhaled medicine. At the moment in the UK, if you have a migraine that lasts for a few days you would be hospitalised and you would be given an injection. Generally that works pretty well but, if it is possible to inhale the medicine rather than having it injected, the treatment setting moves out of hospital and into primary care. So, if a patient has a bad migraine, they can take two puffs of an inhaler at home and have exactly the same profile of response to the medicine as if they had had an injection in a hospital.

We are now taking the concept further and we are developing a product for urge incontinence. It is a similar concept: instead of taking an oral medicine that works for 24 hours but also gives you 24-hour side-effects, we have repurposed the molecule so it can be inhaled. This way it can have an immediate onset of action but also be cleared very rapidly so people don’t have to live with the side-effects.

 

So potentially you are moving to a reliever inhaler for urge incontinence?

Yes, and you can also use it prophylactically. For instance, if someone is going to a very important meeting, they could take a puff and they know that they are covered immediately and for the next one or two hours, but they don’t have to live with the side-effects of the drug for a long period. People are often happy to tolerate the side effects for a short period when they are getting the benefits. Indeed, some of the side-effects of these drugs only really become apparently after some hours. A dry mouth is a common side effect: you’re not going to get a dry mouth within two hours but you will do when you have a long acting drug.

What we are doing is trying to use this particular technology to improve the performance of medicines in certain ways. It is very particular technology for engineering particles. When you prepare particles for inhalation, what you are trying to do is maximise the amount of drug that is going into the lung and reduce the amount of drug that is going to the back of the throat or indeed being swallowed because that then is effectively giving it orally. With our technology, almost three times as much of the drug gets to the deep lung compared with any other way of making an inhaled therapeutic. That’s down to size and also to uniformity – if you can get a really tight size distribution that really helps. It’s also down to aerodynamics: these particles fly at very low pressures and, because they have been precipitated as opposed to being mechanically ground, they don’t have a lot of charge so they don’t stick together or stick to the device and tend to aerosolise very easily This means they reach the deep part of the lung where the drug works best.. The measure used is called the ‘fine particle fraction’. A traditional micronised material might see 23% of the drug reaching the lung. Our technology manages to achieve 69%.

 

Are you turning received wisdom on its head in all this?

I think a lot of the Advanced Manufacturing Supply Chain Initiative projects like REMEDIES are trying to do that. Yes: the received wisdom is still rooted in the pestle and mortar – the apothecary’s way of making something more soluble, more useful and more flowable is to grind it from a big chunk into a fine flowing powder.

But the reality is that that mechanical processes damage materials. And, given that the drug starts with the molecule, why go through all these steps of creating big chunks that you then have to grind down when you can just precipitate the molecule as a single particle? So, when people ask me what we do, I say it’s a little bit like being in the snowflake business. Just as a snowflake has a unique history, that history as it falls to Earth defining its morphology – its shape – the same is true for what we do. We control the precipitation conditions of the molecule and thus can create these functional, highly crystalline and reproducible particles.

 

How has being part of the remedies project help take things forward for you?

In a number of ways. It is a community. It is fantastic for an industry that has typically been quite insular and worried about competition to be working in this way: partners, collaborators, different multinational companies, all offering views as part of the same discussion.

It came at exactly the right time for us because we were, as a small company, having to make some tough decisions as to where GMP manufacturing would have to be. We already had an R&D centre in China. We had some encouragement and support from the Chinese government to locate GMP manufacturing there. Then REMEDIES came along and gave us the opportunity to do that manufacturing in the UK. It has been much the better option for the UK, and also for us as a company because we can more comfortably supply the needs of companies in the global markets from the UK then we could from China. A big goal of REMEDIES has been the re-shoring manufacturing which is fantastic. REMEDIES also allows us to work with very strong scientific partners and institutes such as the Institute for Manufacturing and the Centre for Crystallisation – all of which is a great help to us.