Solubility: Definition and explanation by Pharma Drama
It’s probably the most important physicochemical property of a drug, but what actually is solubility? Pharma Drama is here to give you the solution! In this Snug, we look at the basics of solubility – how it’s defined and how it’s measured.
Watch the video here:
Welcome to Pharma Drama, the channel where we look at the science of healthcare and healthcare products. In this video I want to explain probably the most important concept in the development of medicines – solubility. It’s the first thing that is measured for any potential drug substance, so I think it’s really important to understand what solubility actually means! So, if you’re ready to understand it, make a hot drink, add some sugar, to less than its solubility I would advise, and let’s make a start.
If you look up the properties of a drug substance, you will usually see a statement such as ‘exists as a white, crystalline powder’, and then find a number of properties listed, such as melting point, log P and solubility. The melting point is usually given because it is an easy way to identify a compound, but log P and solubility are much more important in giving an indication of how likely the drug substance is to be absorbed following oral administration. I have a separate video where I discuss log P – the link is in the comments below – because today I want to talk about solubility.
The easiest definition of solubility is ‘the maximum concentration of a given solute that can be achieved in a given solvent’. As we shall see in a moment, the proper definition is a little more complicated than that, but this is a good start. However, to understand the definition, we need to know what ‘concentration’ means.
Imagine we have two different chemical species, both liquids, and we want to mix them together. There are two likely outcomes. The liquids might mix freely to form a continuous phase or they might not mix at all. I have here two liquids; one is ethylene glycol (which is from my car and handily is coloured red) and the other is water. If I mix these together you can see they mix freely to form a continuous phase. If, on the other hand, I take dissimilar liquids – this is olive oil, this is still water – and I mix these together, now you can see that the two phases remain separate, oil on the top and water on the bottom.
What actually happens when we mix two different pure liquids together? We have to break intermolecular bonds and form new ones. Remember that in any material the molecules it contains interact with themselves – when the bonds are very strong we see the material as a solid, when they are not quite so strong we see the material as a liquid and when they are very weak we see a gas. When we mix two materials, liquids in this case, we will only get mixing if the molecules in each material can break apart from each other and form new interactions with the molecules in the other material. Obviously, this is most likely when the two materials have similar chemical properties (this leads to the old adage ‘like dissolves like’). When the two materials have very dissimilar chemical properties it is very unlikely that their molecules will interact with each other and so they remain separate. For liquids, the most important chemical property that governs whether they mix or not is polarity (which is really saying whether the molecules have small electrical charges called dipoles – but don’t worry about that here!). It suffices to know that water is a polar liquid, as is ethylene glycol, which is why they mix, while oil is a non-polar liquid, which is why oil and water don’t mix.
What has this to do with concentration and solubility? The answer is, of course, that these concepts also involve mixing two materials together. They can both be liquids, but more often in medicine we are concerned with a drug (typically a solid) and water. When we add a solid drug to water if they are miscible the drug molecules will interact with the water molecules and dissolve to form a solution. Typically the amount of drug is much less than the amount of water. In other words, the water is in excess and is the majority component while the drug is present as a minor component. We have special terms for this and say that the drug is the solute and it has dissolved in a solvent. The term concentration is simply a way of quantifying how much solute we have in a given volume of solvent. So a typical concentration might be 5 grams per litre, which would mean we have added 5 grams of drug powder to every litre of water. Note here that a concentration is constant, irrespective of how much solution we have. If I made up one litre of a solution at a concentration of 5 grams per litre, and took 100 millilitres of it the concentration is still 5 grams per litre. A lot of students get calculations wrong because of misunderstanding this point!
I hope you might see that we can make solutions of a given solute/solvent mixture of numerous concentrations. I might dissolve 2 grams of drug per litre of water, or 6 grams and so on. Solubility is actually just a special concentration; it’s the maximum concentration that we can achieve. If we have a litre of water and we start adding drug powder to it, initially it will all dissolve. We can add more and see that that dissolves also. But eventually we will get to a point where when we add more drug powder, no more can dissolve and we will see powder particles at the bottom of our container. Remember that to dissolve the solute molecules must interact with the solvent molecules. When all the solvent molecules are interacting with solute molecules, there are no further ‘free’ solvent molecules left to interact and so no more solute can dissolve. We say the solution is ‘saturated’ and the concentration is the solubility.
For example, the solubility of aspirin, which is a white powder by the way, is around 3 grams per litre in water at room temperature. This means if I have a litre of water and I add aspirin powder, if I add less than three grams all the powder will dissolve but if I add four grams of aspirin powder, three grams will dissolve and one gram will remain as solid particles at the bottom of the container.
‘How do we measure solubility?’ I hear you ask? That’s a good question. And the answer is, we do exactly what I just described. We add the drug powder to water (we can, of course, measure solubility in any solvent, but water is most common for drug substances) until no more dissolves and we can see an excess of undissolved powder in the beaker. Why is it necessary to see excess powder? Because if we didn’t, we wouldn’t know the concentration had reached the solubility! And this leads to my final, rather important point. The actual definition of solubility is the ‘concentration of a saturated solution in equilibrium with excess solid’. Right now, please don’t worry why this definition is important – we’ll discuss that in later videos. I just want you to see that in order to measure solubility, we must add solid to water until there is excess solid left over, and that leads to our definition of solubility.
As you might imagine, solubility can be a lot more complicated than I have just described. For one thing, sometimes the chemical properties of molecules can change (say, as the pH changes). Solubility also changes with temperature. But these are issues we can save for another day. I would also note that it does not have to be the case that the solvent is a liquid. We can dissolve a solid solute in a solid solvent (in which case the concentration would be stated as, for instance, 5 grams per kilogram).
But for now, that’s the definition of solubility – the maximum concentration of a solute that can be attained in a given solvent – it’s super-important for drug substances because all drug molecules must be in solution before they can be absorbed and act in the body, so the higher the solubility, the easier it is to dissolve the drug molecules in the body.
Right, I hope you found that brief description useful. If you did, please hit the ‘like’ button and consider subscribing – I will be posting many videos explaining fundamental science concepts and if there are any particular topics you’d like me to explain, please leave a comment below. Otherwise, thank you so much for watching, and I’ll see you again soon.
Source: Pharma Drama