What is dissolution?

An explanatory video by Prof. Simon Gaisford – Pharma Drama

Welcome to Pharma Drama, the channel where we look at the science of healthcare and healthcare products. In this video I’m going to explain the concept of dissolution – the process of a solid dissolving into a solution, which is in fact how I made this lovely cup of coffee. So I suggest you also get a drink and then let’s make a start.

I’m going to start by reminding you what solubility is; Solubility means the maximum concentration of a given solute that can be attained in a particular solvent, usually water in the pharmaceutical world. More formally, it is the equilibrium established between a saturated solution and undissolved solid and I have a short video on solubility that explains this in more detail – click here to access.

In order to reach saturation, or indeed any lower concentration, a solid must dissolve. The process that a solid undergoes when it dissolves is called dissolution. So we start with a solid and a solvent and when we add them together the solid dissolves to reach a particular concentration. If we add so much solid that not all of it can dissolve, we end up with a saturated solution with excess solid, and that is in fact how solubility is determined.

Dissolution can be considered to have two steps. In the first step, molecules must break away from the surface of the dissolving solid. Assuming that the dissolving solid is a crystalline material, the lattice energy holding the molecules together in the solid state must be overcome in order for a molecule to break free. Since energy is needed to break these bonds, this process is endothermic. Think about what happens when you heat up a crystalline material. At a particular temperature the material gains enough energy that the bonds holding the molecules together are overcome and the material melts. We call that the melting temperature, and it varies for different materials because the strengths of the bonds in the crystal lattices are different. I hope you can see, therefore, that because this first stage of dissolution, breaking molecules away from the crystalline solid, is the same as melting, the amount of energy required to break all of the molecules apart is the same as the energy required to melt it. This energy is given a special name – the enthalpy of fusion.

We have discovered something interesting already! The first stage in the dissolution of a solid is essentially the same melting. This has some interesting consequences. One is that it implies that solids with different melting temperatures may dissolve differently. Since two polymorphs of the same material will have different melting temperatures it is then very likely that they will dissolve differently, and this has a lot of consequences for drug development! Another, which you may already be thinking of, is that amorphous materials should dissolve rather fast, because they do not have a melting point – and again, this turns out to be true! One of the main reasons amorphous materials dissolve so fast is that there is no lattice energy to overcome.

In the second step of dissolution molecules that have broken away from the surface of the dissolving solid are surrounded by molecules of solvent – this is called solvation. The solvent molecules actually form weak bonds with the solute and so when you think of a molecule dissolved in a solvent, you should really think of a molecule with a shell of solvent molecules that moves as one discrete entity. This means that some of the solvent molecules become ‘tied’ to the solute molecules and are no longer able to behave like the bulk solvent. This is where the concept of solution ‘activity’ comes from, and is why it is different from concentration, as I shall discuss in a later video. For now, it suffices for you to know that when a molecule dissolves in a solvent it has a shell of solvent molecules around it. Once solvated, the solute molecule diffuses away from the surface of the dissolving solid into bulk solution.

I think you might imagine that whether the solvent and solute molecules ‘like’ each other is very important at this point. And by ‘like’ I really mean can the molecules form bonds or can they not? If they can form bonds, the interaction between them will be energetically favourable. Energy will be released and the process of solvation will be exothermic. If they really don’t want to form bonds the interaction between them will be energetically unfavourable and the process of solvation will be endothermic. In either case there will be an energy change when solvation occurs, which we term the enthalpy of mixing.

What does this mean for dissolution overall? We can consider the overall energy of the process as the sum of the enthalpy of fusion (step 1) and the enthalpy of mixing (step 2). We call the overall energy the enthalpy of solution. For dissolution to proceed well, we really want the enthalpy of solution to be large and negative (it can be positive if there is a large change in entropy, but that is a discussion for another day). As I said already, the enthalpy of fusion must be positive for a crystalline material and will be zero for an amorphous material. Thus, in order for dissolution to be favoured, we want the enthalpy of mixing to be large and negative. Where there is a strong, energetically favourable interaction between solute and solvent this term will be exothermic (negative) and dissolution should proceed. Where there is an unfavourable interaction the enthalpy of mixing will be endothermic (positive) and dissolution will be slow (or not proceed at all!). Dissolution should be fastest for an amorphous material because the enthalpy of fusion will be zero.

If thermodynamics isn’t your thing, try and visualise the process like this; molecules must break free from the solid and that means energy must be put in. That is always unfavourable. Then they must form bonds with the solvent. If they can form bonds easily they will rapidly get solvated and disappear into solution. If they don’t form bonds with the solvent then they won’t get solvated and everything stops.

Since there are two steps to dissolution, one will usually be slower than the other and will be the rate-limiting step. If step 1 (breaking of bonds) is the slowest then we have interfacially-controlled dissolution and if step 2 (solvation) is the slowest we have diffusion-controlled dissolution.

Right, that is all we need to consider about dissolution for now. There are some other things that arise from what we have just discussed – for instance, ideal solubility, kinetic solubility and the change in solubilities for different polymorphs, but we will discuss those in other videos! For now, just remember that in order to dissolve a molecule must break free from a solid and interact with the solvent and so whether this happens well or not is simply a balance of these steps. If you found that description useful, please hit the ‘like’ button and consider subscribing – it really helps the channel. Otherwise, thank you so much for watching, and I’ll see you again soon.