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Develop Better Cosmetics Via Science-based Formulation Using HSP

Steven Abbott – Mar 29, 2018

Cosmetic Active Delivery - HSP How do ingredients in a skin formulation interact with each other and the skin? You need to know the answer to ensure that the ingredients are compatible and to optimize for controlled delivery of an active through the skin.

A good way to approach such questions is via Hansen Solubility Parameters which, though simple, give a science-based approach to such solubility and compatibility issues. With such an approach your problems can be resolved much faster, with fewer trials and better outcomes.

Here, Professor Steven Abbott explains what Hansen Solubility Parameters are and how they should become a go-to tool for science-based formulation in cosmetics.

Let's get going...




Better Cosmetics via Science-based Formulation using Hansen Solubility Parameters (HSP)


So you need to know if your cosmetics ingredients are mutually compatible, or you need to optimize the solubility of a key active or want to know if ingredients are compatible with the skin. The trick is to use the minimum effort while getting the best possible outcomes.

To understand the different solubility and compatibility issues between your components you might be using vague words such as “hydrophobic/hydrophilic” or “polar/non-polar”. Unfortunately, these are too vague and aren’t at all numeric. When you read sentences like “The API was hydrophobic so we dissolved it in ethanol” you wonder what word they have for a molecule that dissolves in heptane.


How to do it?


We need numbers to formulate scientifically. What we especially need is a measure of the “distance” between any two molecules, to tell us how “like” or “unlike” they are. To do this we must start with three numbers that describe each chemical, polymer or excipient used in the formulation.

Why three? This is because two is too small and four is too complicated. For cosmetics, the molecular size is also important and is a natural part of the HSP landscape.

Formulating Science-based FormulationsWe start by finding out:

  1. What those three numbers are
  2. How you can measure or estimate them
  3. How you can use them in three specific areas of cosmetics

The three specific areas of cosmetics include:

  • Finding or determining the HSP values of the ingredients used in a cosmetics formulation
  • Ensuring compatibility between these ingredients
  • Optimizing for controlled delivery of an active through the skin


The 3 Hansen Solubility Parameters


We want three numbers to capture three key, familiar features of any molecule: the Dispersive, Polar and Hydrogen-bonding aspects.

The Polar and Hydrogen-bonding aspects are familiar to formulators. The Dispersive part is not so familiar but is not a problem. It is the general (van der Waals) interactions holding all molecules. Molecules with no polar or hydrogen-bonding capabilities are held together either with a broad electron cloud (e.g. aromatics) that self-interact strongly or a tighter cloud (e.g. alkanes) with weaker interactions.

The three numbers are, respectively, δD, δP and δH and are the Hansen Solubility Parameters (HSP), developed 50 years ago by Dr. Charles Hansen.

Find the values of HSP parameters of some common solvents in the table below:

Solvent δD δP δH
Acetonitrile 15.3 18 6.1
Acetone 15.5 10.4 7
Benzene 18.4 0 2
Diethyl Ether 14.5 2.9 4.6
Dimethyl Sulfoxide 18.4 16.4 10.2
Hexane 14.9 0 0
Ethyl Acetate 15.8 5.3 7.2
Ethanol 15.8 8.8 19.4
Methylene Dichloride 17 7.3 7.1
N-Methyl-2-Pyrrolidone 18 12.3 7.2
Tetrahydrofuran 16.8 5.7 8
Water 15.5 16 42.3


From this list of HSP of some common solvents, you will have no problem understanding the broad trend of the numbers makes.

  • Acetonitrile has a high δP value as we would expect from its high dipole moment. However, its δH value is not very large because it does not engage in strong hydrogen-bonding. Ethanol’s δP value is relatively large, but it has a larger δH value, and we would expect the same from this strongly hydrogen-bonded solvent. The δD values of both those solvents are relatively modest.
  • Benzene and DMSO both have higher δD values because of the large electron clouds surrounding them
  • Hexane just has a low δD value, while and ethyl acetate and acetone are middle-of-the-road in all their values.


Calculating the Distance between Two Molecules


Now we are set to find how “like” two molecules are. To calculate the “distance”, D, in 3D space between any pair, we use the famous HSP formula (including a factor of 4 for the δD values)

D² = 4(δD1-δD2)²+ (δP1-δP2)²+ (δH1-δH2)²


  • If D is less than, say, 4 then, this is a reasonable match, while values greater than, say, 8 represent a poor match.
  • If you have a target molecule plus a list of molecules which, for other reasons, you might want to use with the target, you calculate D between the target and each of the molecules.

Producing a Good solvent in HSP SphereAfter sorting them from low (good) to high (bad) you will find a small group of low D molecules from which you can select according to other priorities, such as cost or greenness. A typical example would feature a polymer, as the target is a polymer along with a list of the common excipients or solvents. Or the target could be an API and, again, the molecules could be excipients. HSP also work very well when you want to disperse pigments or nanoparticles (e.g. hydroxyapatite) within a formulation.

HSP can also solve another tricky problem. Suppose there is no single molecule that meets all your requirements. You can create a rational blend between two unsuitable molecules (each of which has a high D value), but which you like to use for other reasons. Suppose each molecule has a reasonable match of δD and δH with your target but have a large D because one has a low δP and the other has a high δP. The HSP of a blend is the weighted average of the HSP values of the components, so in this case, the δP can be tuned to enable a close match to the target.

This means that a blend of unusable molecules that are too unlike your target (high D) becomes usable. This ability to create great blends from inadequate starting materials is one secret of HSP’s success over the past fifty years.

Given that to do all these calculations require that you know the HSP values, but where do you find them?


Finding the Parameters


Fortunately, the parameters are known and in the public domain for all the common solvents, many of the newer green solvents and for many polymer additives and cosmetic excipients.

What about your own special chemical, polymer, excipient, additive? The answer is that HSP values can be measured via two techniques, each of which you can do in-house or contract out to those set up to do it on a regular basis.

  1. The first technique involves your judgment of whether your material is “happy” (soluble, swellable, dispersable …) or “unhappy” in a set of solvents that cover HSP space. The center of the sphere is the HSP. The sphere’s radius defines the range of solvents that are going to be usable.

  2. The second technique is based on Inverse Gas Chromatography (IGC). This measures how strongly or weakly each of a set of probe solvent molecules interacts with your sample which provides the stationary phase of the IGC column. It is the standard technique is the most widely used for polymers, APIs and particles. The IGC technique is especially useful for the cosmetics world where oligomers, surfactants and excipients are so fluid at room temperature that the standard test gives too many “good” solvents and too few “bad” ones.


Create a 'Happy' Formulation!


Given that so many cosmetic formulations are delivered as emulsions, who cares about the mutual solubility of the ingredients other than water? The answer is that formulators should care. The key fact about most formulations is that they are on the skin for many hours, yet most of the water in which they were delivered has evaporated in 15-20 minutes.

So it is important to know what will happen to the ingredients once the water has gone. If, for example, they phase separate unexpectedly then this will change the long-term “feel” and may have a negative impact on the delivery of the key additives. This means that the mutual HSP Distances between the ingredients should be known and juggled to give the right balance of solubility.

Create a Happy Formulation Once, an ingredient list of a skin delivery formulation was presented to me, which to the surprise of the formulators, showed zero delivery into the skin. What had gone wrong? A “small” percentage of the overall formulation was a surfactant. But once the water had gone, this was a large percentage of the remaining formulation. As a large molecule it could not penetrate into the skin so remained on the surface. And there was an excellent HSP match between the active and this surfactant. The active was sitting happily on top of the entire skin in this comfortable environment: why would any of it ever go into the skin?!

By knowing the HSP of your additives from your suppliers or by measuring the values for your own special ingredients, it becomes much easier to create “happy” formulations where most things are happy to be with everything else. If the active is too “unhappy” it might simply crystallize out and be of little use. If it is too happy in slow-diffusing ingredients, then it will stay on top.



Optimal Skin Delivery


Classic experiments by Hansen and consistent observations since then have confirmed that skin has an effective HSP of ~ [17, 8, 8]. If we treat it as a typical polymer then solvents in that region of HSP space will swell it, increase the diffusion coefficient and enhance permeation of the active, if the active is also soluble in such solvents.

This confirms to the well-known distrust that chemists have of DMSO; it is not very toxic on its own, but it swells and passes through the skin very quickly and can take many toxic chemicals with it.

For skin delivery, therefore, it is important to know which ingredients are capable (low HSP Distance) of swelling the skin and also of dissolving (low HSP Distance) the API. Usually, there is a trade-off; a perfect solvent for the API might be too far from skin and vice versa. A smart balance is needed.

And, speaking from experience, I can warn against trying to be too good. I once tested a new skin formulation on my face, using dimethyl isosorbide which is proving to be a popular skin ingredient because of its close HSP match to the skin. An hour or so after applying the test formulation my skin was stinging so badly that I had to stop the experiment and wash off the formulation.

The cause of the problem quickly became clear. The DMI went through the skin far faster than the large API molecules. These got stranded on the skin and crystallized out when most of the DMI had gone. Their natural crystal form was as needles – and these are what caused the stinging sensation. A rational reformulation keeping not just a good match, but using somewhat slower solvents, quickly solved the problem.


Conclusion


For more than 50 years, HSP has proven themselves in the world of formulations. Common tasks such as finding good solvents (or blends) or ensuring compatibility between components in a formulation become much more rational and efficient when the HSP of all the key ingredients are known, either from your suppliers or internally, and HSP Distance calculations are used routinely to find the best combinations.


Know More about HSP!


Avail a powerful combination of software, eBook and datasets by Steven Abbott, Dr. Charles Hansen and Dr. Hiroshi Yamamoto - Hansen Solubility Parameters in Practice (HSPiP), at an affordable price. It is used all around the world by formulators to obtain HSP values for thousands of chemicals.

Also, explore video tutorials to enhance your knowledge on HSP on the official Hansen-Solubility site - www.hansen-solubility.com.



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