23 Mar 2015 Solubility theories: S-Class Mercedes, Landrovers and hovercraft.
Last week I spent two days at a symposium run by COSMOlogic celebrating 20 years of the COSMO-RS methodology for calculating solubility properties. As it happens, I was asked to give the opening talk for the symposium and chose the topic Solubility theories for the real world: Current capabilities and future needs. This gave me plenty of scope to explore what is happening in the world of solubility theory
My personal view is that COSMOtherm (the core of the COSMO-RS suite of programs) is the best solubility software on the planet. It is immensely powerful and over the years has become steadily more accurate and capable of tackling ever tougher questions. In the symposium there were talks pushing the boundaries of ionic liquids, micelles, chemical reactivity, toxicity predictions and much more. To me, COSMOtherm is the S-Class Mercedes of solubility software, effortlessly cruising on the Autobahn of solubility studies.
However, as I'm co-author of HSPiP, Hansen Solubility Parameters in Practice, I also have a view that the most useful software on the planet is HSPiP. The theory is much simpler than that behind COSMO-RS and it cannot hope to be as powerful. But on the other hand it is a sort of Landrover of solubility tools - able to deal with all sorts of rough terrain that COSMO-RS, as a "pure" theory can't handle.
Whether I'm right or wrong in my judgements scarcely matters because there are three huge issues facing the world of solubility science. The first issue is that the vast majority of people with solubility issues have no idea of any relevant solubility theory. Most go through their formulation lives thinking that "hydrophilic/hydrophobic" or "polar/non-polar" are pretty good ways to analyse solubility, or if they want a number use the infamous LogP. This is very sad. Ignorance of solubility theory means vast amounts of wasted formulation work. I've met countless examples of hard working scientists who have tried to formulate in a hopeless part of solubility space with no idea that it was hopeless and who have, predictably, failed.
The second issue is that many problems that don't, at first, look like solubility are strongly dependent on solubility science. Take, for example, "flavour scalping", the loss over time of some flavour components through (or into) the packaging of the food or drink. The loss is a "diffusion" problem, which is governed by Fick's laws of diffusion. The diffusion depends on a diffusion coefficient which is governed by the packaging polymer and the shapes/sizes of the different flavour molecules. But it also depends on the solubility of each flavour molecule in the top 1nm of the polymer because the larger the solubility, the larger the concentration gradient which drives the diffusion. So many "diffusion" problems are, in fact, "solubility problems". See the Flavour Scalping example on the Hansen Solubility website for more details.
The third issue is more fundamental. Many "solubility" issues are in fact "solubilization" issues. It is common for formulators to solubilize molecules (drugs, cosmetics, flavours...) using "hydrotropes" or "solubilizers". There are many problems mixed up in this area.
- People use the same word, e.g. "hydrotrope" to describe many different physical phenomena.
- Many of the "explanations" for hydrotrope or solubilization effects are simply wrong.
- Classical solubility theories like COSMO-RS and HSP are invalid for many of these effects which depend on local loose structures and associations.
Because this area is such a mess I've created a website Practical Hydrotropes to at least attempt to bring some order into the chaos
So there's a lot to be done in the world of solubility. Tools such as COSMO-RS and HSP will continue to be developed and refined. But more importantly, the huge majority who know nothing about solubility theory need to be brought up to speed with the basics. That's why I've created Practical Solubility with some of the basics made easily available. And we need new tools for understanding hydrotropes and solubilizers. I've written 3 papers with Dr Seishi Shimizu of U. York where a lot of clarity on basic hydrotropy has emerged (and old explanations comprehensively refuted) and my hope is that this will open fresh pathways into this largely uncharted territory. Perhaps for this area we need the solubility equivalent of a hovercraft!