Materials masterclass: Plasticisers in amorphous solids (glasses)

In this video Pharma Drama aka Prof. Simon Gaisford explains why amorphous pharmaceuticals are so unstable when there’s water around. It’s because water is an excellent plasticiser, and speeds up the rate at which amorphous materials relax, ultimately leading to crystallisation. Plasticisers are also added to all sorts of plastics and polymers, to change their mechanical properties and feel to the touch. But what are they? And how do they work? Well, that’s what we’ll discuss in this video!

See the video and read the full transcript below.

Read the full video transcript here:

Welcome to Pharma Drama, the channel where we look at the science of healthcare and healthcare products. In this video we’re going to consider the stability of amorphous glasses, with the classic example of candy floss (or cotton candy if you’re in the US). Before we start, though, let me show you this video which I filmed in my lab. It shows two samples of candy floss, from the same batch, on watch glasses at a constant temperature. You can see that one of the samples collapses while the other does not. The only difference between the two is that the sample that collapsed was not covered but the sample that didn’t collapse was covered. So what’s happened? The answer is that the sample that collapsed became plasticised. Clearly, then, plasticisers are very important to the stability (and mechanical properties) of amorphous materials. But what are they and how do they work? Well, that’s what we’re going to discuss. So get yourself a drink, which ironically would make an excellent plasticiser – I unsurprisingly have coffee – and let’s make a start.

Very clearly the only difference between the samples in my video is that one sample was exposed to the atmosphere and one wasn’t. Therefore, we can say straight away that there must be something in the air that is reacting with the candy floss, causing it to collapse. What do you think that might be? I’ll give you a second to think about that. Got an idea…? There aren’t too many options to be fair. It’s unlikely to be oxygen or nitrogen so that really only leaves… water. Yes, it’s the water in the air that interacts with the candy floss and causes it to collapse.

Now, to help convince you that water is the issue, I filmed another video with two samples of candy floss but this time in an air-conditioned lab – However, it was a rather boring video! Nothing happened in fact. Why? Because air-conditioning units have the effect of drying the air, so there’s much less water available.

So water appears to affect the stability of amorphous glasses. But why? Well, to answer that we need to think about that diagram I keep referring to when I talk about how amorphous materials form. Yes, that one. And incidentally, if you’re not familiar with that diagram, I’ve put links to the videos where I explain it in the description below.

You’ll remember that an amorphous glass is actually a high viscosity liquid. That is, it’s a material with the molecular structure of a liquid (a random arrangement of molecules) but the viscosity of a solid. The high viscosity means that the rate at which the molecules can move within the glass is very low, and so the glass is reasonably stable. And the lower the temperature that the glass is stored below the glass transition temperature the slower the molecular mobility, so the more stable the glass.

So far so good.

But although the rate of movement of molecules in the glass is low, it’s not zero. So over time, and that can be long – say days, weeks, months, the molecules will move and movement will always occur in the direction of greater alignment (which means lower energy or volume). Hence with time a glass will relax, travelling along this line on our graph. Eventually, then, the molecules will align perfectly and the material will crystallise.

Water in the air makes the process of relaxation faster – usually much faster! – which is why we saw the sample of candy floss collapse in my video. The molecules were able to move faster and faster, and hence were able to crystallise. This is why I said the sample collapsed – the volume of the crystalline phase is much lower than that of the glass.

But how and why does water cause this effect, which we call plasticisation for reasons I’ll come back to in a moment? The answer is two fold. Firstly, water molecules are very small – much smaller than that actually! – they only have one oxygen atom and two hydrogen atoms remember – and so being small they are able to be absorbed by amorphous glasses. This is helped by the fact that the molecules in glasses are randomly dispersed and so the volume of the glasses is large – that must mean there are bigger gaps between molecules in a glass than in a crystalline phase, and so that creates room for the water molecules. Secondly, increasing the water content of a material is a bit like diluting it. Imagine you had a some really thick honey in the kitchen – too thick to pour in fact. If you added a bit of water to dilute it, it would become thinner and easier to pour. What you’ve actually done by adding water is reduce the viscosity of the honey.

And that’s exactly what water does to amorphous glasses when it is absorbed. It dilutes the glass and reduces its viscosity. Now, if you think back to how I explained the formation of amorphous glasses in the first place you’ll remember I said that as the temperature of a supercooled liquid is reduced, it occupies an ever decreasing volume and so its viscosity increases. The glass transition temperature is the point at which the viscosity becomes so high the sample feels like a solid.

I hope you can see, therefore, that by absorbing water the viscosity of the glass is reduced and that MUST have the effect of allowing the molecules to move more quickly. And since movement of molecules is what happens during relaxation, absorption of water must increase the rate at which relaxation occurs.

If only a small amount of water is absorbed, for instance when the relative humidity of the air is low, the rate of relaxation is not increased significantly and the glass remains stable. But as the amount of water in the air increases more and more water can be absorbed and the rate of relaxation increases a lot. At a critical point the rate of relaxation becomes so high that the sample crystallises and that is what happened to my candy floss sample.

This means that there is often a critical relative humidity value, below which a glass remains (relatively) stable and above which the sample will crystallise. We term this the critical relative humidity, and we can determine it with dynamic vapour sorption (or DVS), as I’ll show you in a separate video.

All of this suggests that water, and hence plasticisers in general, are rather bad for the stability of amorphous glasses. And that is generally true for pharmaceutical materials, because they are usually comprised of small molecular weight organic compounds that really do want to crystallise – all they need is a little help.

It’s not true, however, for other amorphous materials more widely. In fact, plasticisers are essential to almost any material made from plastics. Why? Because plastics are really polymers, and as you know polymers are chains of molecules joined end to end. The molecular weight of polymers can become very large, and their chemical properties can be tailored to specific applications. Are polymeric materials amorphous or crystalline? Now there’s a question for you!

What do you think? Mmm…. The answer is that they are usually amorphous, sometimes partially crystalline but hardly ever completely crystalline. Why? Because to crystallise all the molecules in a material must align in a perfectly structured, repeating pattern and when the molecular weight becomes high that’s just about impossible. So polymeric materials are almost never crystalline. But it is possible that within the polymer small sections align, which is when we say a material is semi-crystalline.

This has a number of consequences – for one, a polymeric material will be a very stable amorphous material, because it can’t crystalline! Secondly, the mechanical properties of polymeric materials can be changed a lot if it can be semi-crystalline, as I think you might imagine. But also, because they can’t crystallise, we can add plasticisers to polymeric materials to change their mechanical properties, safe in the knowledge we won’t cause them to crystallise!

Adding plasticisers to polymeric materials usually has the effect of making them feel softer and more malleable – because, as we just discussed for water, plasticisers have the effect of disrupting polymer-polymer interactions and lowering the viscosity of the material. And this is why they are called plasticisers – they make materials, polymers in particular, feel more plastic! So manufacturers fine tune the feel of their materials by adding plasticisers, so they feel pleasant to the touch.

Is the most common plasticiser added to plastics water? Definitely not! Many plastics are not water soluble, so won’t absorb moisture, and even if they did there is always water in the air so the actual water content of the plastic would constantly be changing, altering the feel of the material.

Rather, small organic compounds are used as plasticisers – things like phthalate esters or aliphatic dibasic esters, polyesters and citrates. They are selected based on miscibility with the polymer being used and the final feel of the material you are trying to achieve.

Have you ever got into a brand new car and thought to yourself ‘Mmmm, I love that new-car smell!’? Well, what you are actually smelling, predominantly, is the plasticisers that have been added to all the plastics! That’s because, as you might have guessed, being small molecules plasticisers are typically quite volatile, so will vapourise. Hence that new car smell is really a cocktail of organic compounds! Nice. It’s also why when they get older cars lose that new car smell and the plastics inside become hard and crack – they have lost their plasticisers and so have become brittle.

And finally, what would happen if we added a compound that disrupted polymer-polymer bonds but formed stronger interactions, rather than weaker ones? We would make our material mechanically stronger and we call these compounds anti-plasticisers.

Right. Who knew we’d start this video discussing with wet candy floss and end up inside a new car? Well I did to be fair because I wrote it didn’t I? But that should tell you the importance of plasticisers. All you really need to remember though is that a plasticiser is a small molecular weight organic compound that can mix with an amorphous material, disrupting intermolecular bonds and lowering the viscosity. This causes an increase in the rate of movement of molecules, making relaxation faster. For amorphous materials with a large molecular weight this will change their mechanical properties and for amorphous materials with a small molecular weight this will tend to cause crystallisation. Water is an excellent plasticiser for pharmaceutical materials, which is why amorphous pharmaceuticals are usually unstable with respect to humidity.

Hopefully you found that useful. If you did please hit the like button, subscribe if you haven’t already and please tell your friends about the channel – all of that really helps. Otherwise, thank you so much for watching and I’ll see you again soon

Source: Simon Gaisford, Materials masterclass: Plasticisers in amorphous solids (glasses) – YouTube

Read also others Simon Gaisford articles here:

Unlocking the Mystery of Glass Transition Temperatures – Explainer video by Pharma Drama

excipients formulation