Preservative Adventures with Sodium Levulinate and Sodium Anisate

Sometimes things don’t always work out as you expect. This is a story about that.

One of my favourite natural preservatives at the moment is a blend of glycerine with Sodium Levuninate and Sodium Anisate.  I love it because it is clear, colourless, odourless and high performing.  I’ve put a few formulations through Preservative Efficacy Testing with this preservative and had them pass – creams, spritz, cleansers (gel and emulsion based) and masks – so my faith in this little beauty is grounded in science which re-assures me.

So what’s odd then?

Well it turns out that I forgot to adjust the pH down on one of the products I just got results back for so the resting pH was 6.15 instead of the pH 5 that I wanted it to be.  I usually adjust the pH of my formulations containing this ingredient because the manufacturer says that the product works best in acidic conditions.  It’s not that pH 6.15 isn’t acidic – anything less than pH 7 is acidic – more that the pKa value of Levulinic Acid is 4.61 so at pH 6.15 it would be almost 100% salt, not acid and I’ve been told it is the acid that has the preservative action rather than the salt.

Aside disk of pKa. 

All of the acids we use in cosmetic science are ‘weak’ acids and as such exist in a mixture of their salt and their acid form. The point at which both acid and salt forms are in balance is acids pKa value. Above the pKa (more alkali) the acid will exist mainly as the salt and below, mainly as the acid. At the pKa it’s 50:50.  A change in pH of 1 jumps the ratio up very quickly, so that around 90% of the ingredient is in its acid or salt form depending on if it jumps up or down.  So for Levulinic Acid a pH of 5.61 means 90% Salt whereas a pH of 3.61 is 90% Acid.

The PKa value is a constant and each acid has one, some have more (such as citric acid).

And back to the oddness of what’s going on in my formula

But then again, the manufacturer does say that the Sodium Levulinate/ Levulinic Acid can work between pH 4-6 while the p-Anisic Acid/ Sodium Anisate work between pH 4-6.5.

So maybe pushing a pH of around 6 isn’t so bad after all.

Especially given that my  pH 6.15 product passed PET. 

On another note some stability testing I’ve been doing on a formula using this preservative have also showed the pH to rise from 6.15 – 6.45 over 16 weeks in the oven (equivalent to around 15 months real-time) and that has been playing on my mind – are these products now un-preserved? I need to get them micro-tested to check….

So I had a look into the science and found that Sodium Levulinate is commonly used as a meat preservative.  In this patent here you see the pH of the samples tested are between 5.8 and 6.23 and the preservative worked well in all cases in spite of the fact that even at pH 5.8 we have only around 55% as Levulinic Acid.  This paper talks about Sodium Levulinate being the preservative rather than levulinic acid and this paper found that Levulinic Acid produced disappointing results when compared with Lactic or Acetic acid for meat washing – a bit of a web search on google scholar confirmed my suspicions that it is the Sodium Levulinate that is used more than the Levulinic acid.

There is another reason why I’m insanely interested in this is solubility. 

At pH below 5.5 the above blend does indeed switch from its salts to its acids, you can see that visibly as while the salts have good water solubility the acids do not. As the pH reduces the preservative starts to form little white crystals if it is in a water-dominant formula, this wouldn’t be such a problem in an emulsion as the acids would usually find something else to dissolve or disperse into but if your product is predominantly water there will be trouble!

From what I’ve looked at, got results on (PET) and seen with my own eyes a pH of 6 in a water-dominant product is probably fine and will allow for the use of this preservative without fear of the preservative coming out of solution.  Lower the pH and you will have a problem, not necessarily with preservation but with product clarity.

But what about the rise in pH over time?

I suspect that what is happening, and especially in the presence of a catalyst such as heat, is that there is a shift towards the salt formation over the acid form. I suspect this because the starting pH of the preservative is between 7-8.5 (mine was pH 8 @ 18C) and the ability of the reaction to go both ways.  Whether this impacts the long-term micro stability of the product is yet to be seen (or measured). The only thing I can say is there must be a reason the manufacturer gives a cut-off pH of 6.5. But what is I wonder?

Micro contamination typically reduces the pH of the product as the microbes produce CO2 as a bi-product of respiration.  This CO2 acidifies the environment which could, at least in theory, push the equilibrium back towards the acid form (for the preservative) and therefore more within the target range of action. That said, one wouldn’t want to wait for micro contamination to bring the pH down, a buffer solution would be a better idea!

Overall  I think  there is enough evidence to say that the salt form of both actives are effective preservatives and that the pKa values of these ingredients is, for whatever reason of minor importance for this application.  Ignoring the pKa values is something I’m fairly happy to do but even though it makes no logical sense given what I’ve said above to stick to the manufacturers guidelines of max pH 6.5 I am lacking the real-time evidence at this point to back that up.   What I would say though is that in a cream formulation a very water-soluble preservative would be un-desirable as it would leave the interface between the oil and water vulnerable.  So, it would make logical sense for the pH to be lower to reduce the water solubility (by increasing the percentage of the preservative that is in the acid form) and thus keep the preservative at the interface.  This is irrelevant in a water-only or water-dominant formulation where the contamination risk is predominantly in the water phase.

Picture below:

At low pH (below 5.5) the salts in this blend change to their acidic form. The acids have low water solubility as we can see here with the precipitate that has formed.  This is a problem in a water-dominant formula but is less so in an emulsion as the acids can better disperse in a multi-phase system. 

So yet again something that I took for granted as being simple has potentially turned out to be quite different indeed.

I might well try the preservative at pH 8.5 in a water-dominant formula to test this theory (I know that one sample doesn’t constitute a good scientific trial but it’s a start).  I could also try a cream formula at pH 7 to see how that fairs (my other creams have been at pH 4.5 and pH 5.2 and passed).

But for now that’s that.

Thinking about stuff is always exciting and very interesting wouldn’t you agree?