From ibuprofen and paracetamol to antibiotics and antidepressants, medicines have made our lives healthier, easier and longer. Over the last 50 years, in the European Union we’ve grown used to having quick and easy access to medicines. This contributes to our quality of life, and extends our life expectancy. Overall, the use of medications in the European Union is on the rise. However, have you ever thought about the environmental impact of the pills we take? We certainly have, and we want to do something about it. Keep reading, this article will explain some of the motivations behind IMPACTIVE.

CO₂ emissions and waste of the pharmaceutical industry

When we talk about climate change and industry, we usually think of companies in the petrochemical, aviation and automotive sectors. However, if we calculate carbon emissions adjusting to revenue, pharma comes up high on the list – and on top of the automotive industry, for example. Specifically, pharma emits 48.55 tonnes of carbon dioxide equivalent (CO2e) for every million of dollars generated. This is 55% greater than the automotive sector, at 31.4 tonnes per million dollars. In the case of pharma, these emissions are mainly connected to the manufacturing stage: we use a huge amount of energy and resources to produce drugs.

And greenhouse gas emissions are only the beginning. There are additional issues. For instance, making medicines also consumes a lot of water that is then discarded, and generates waste materials like the solvents used in the reactions and purifications. To give you an idea, producing only one kilogram –or two pounds– of an active ingredient generates 182 kg of waste. Surely, there must be a cleaner way of manufacturing medicines. And yes, there is. But it requires changing the way we work – we must rethink how the pharma industry manufactures medicines.

Switching to a greener chemistry: mechanochemistry

Solvents are a big part of the chemical reactions carried out  in the pharma industry: up to 80 out of 100 kilos of the substances mixed in the reactors are actually solvents – much like 80% of your coffee is just water. Currently, solvents are both a blessing and a curse. They’re a blessing because they enable the chemical reactions that yield the ingredients we need. And they’re a curse because solvents are one of the main sources of waste – plus they’re often toxic and hard to dispose and recycle. Therefore, when solvents are managed badly, they can have disastrous consequences. Luckily, there’s a set of techniques to get rid of solvents completely: it’s called mechanochemistry.

Mechanochemistry mashes molecules together, using physical forces. By doing so, it minimises the use of solvents – and sometimes avoids solvents altogether. Instead of using big vessels for the reactions, mechanochemistry uses ball mills, grinders and extruders to bring the reactants together and produce the chemical reactions. 

Another advantage of mechanochemistry is that it usually requires milder reaction conditions, avoiding extreme temperatures and pressures. Mechanochemistry reduces  energy consumption, bringing down the associated CO₂ emissions as well. Let’s look at an example. One of the essential medicines listed by WHO is nitrofurantoin –an antibiotic mainly used to treat and prevent lower urinary tract infections, such as cystitis. In 2022, a study by IMPACTIVE researchers and collaborators compared two ways of producing nitrofurantoin: the “traditional” way, and the mechanochemical way, using a method called twin-screw extrusion. The team found an overall reduction in key metrics: nearly a 90% less for indicators such as ecotoxicity, CO2e emissions and operating costs. So, not only is mechanochemistry better for the environment, it’s also cheaper!

These are the basics that motivate our project – IMPACTIVE. But, what are we going to do, exactly?

IMPACTIVE: Getting rid of solvents by mashing molecules

In a nutshell, we’ll go by the title: we’ll manufacture drugs using mechanochemistry – mashing molecules. More specifically, we want to manufacture the functional compounds within the pills and tablets we take: the Active Pharmaceutical Ingredients, or APIs. Among the many ingredients of drugs, APIs are the molecules responsible for the healing effects of medicines.

To do this, we will look into several different techniques: 

• Ball mills: a type of grinder, made of a big vat that contains balls inside. Once the materials are inside, you spin the vat, and the collisions and clashes between the balls and the reactants cause the chemical reactions. Depending on the process, we use ball mills with different geometries, as well as  balls of different materials and sizes. 
• Twin screw extrusion: two screws mounted in a barrel, and the thread of the screws interlock with each other. In this way, the reactants move along the screws, whichmash the molecules together as they spin.
• Resonant acoustic mixing: an innovative technique that uses… sound! Soundwaves of specific frequencies move molecules, and mix and mash the reactants. It’s a vibrant field! 

These are the main techniques that we will explore, but we will also take a look into others, like spray drying, bed milling, and different types of extrusion.

Of course, none of this wouldn’t make sense if the methods can’t be applied to industry and manufacturing. That’s why at IMPACTIVE we have specific partners to ensure that lab reactions also work when scaled up to industrial settings. Our teams will analyse the most promising approaches, identify the main barriers for scale-up and come up with ways of taking the reactions out of the lab and into industrial plants.

While mechanochemistry is overall a greener chemistry than usual, we also have to keep the environmental impact in mind. That’s why part of our team is specialised in Life Cycle Analysis (LCA): a technique to study the whole lifespan of manufacturing processes, getting data about their overall environmental impact. And this goes beyond CO₂ emissions: we look into the toxicity of the materials,the amount of waste generated, the energy consumed… In this sense, IMPACTIVE has two main pillars:

• Safe by design: an approach towards pharma manufacturing that has safety at the centre. This means minimising waste, as well as minimising the use of harmful reagents and intermediates. So, we always choose the process with fewer toxic products – or, ideally, none at all.
• Manufacturing analysis: we look into the manufacturing process of the APIs, and analyse their impact and requirement under many different lenses. Their energy consumption, the environmental impact of the waste generated, the carbon and greenhouse gas emissions … and as well socio-economic aspects, like the operating costs. This provides us a thorough comparison between the new techniques and. the processes currently used by pharma companies.

Our plan is doing this for several molecules and APIs: drugs with different effects, including antidiabetics, anticancer and antihypertensives. IMPACTIVE is at its initial steps,but stay tuned to our social media (Twitter and LinkedIn) to get our updates!