Do Sodium Citrate or Betaine react with Salicylic acid?

toketsu

Hi!

Thanks to this forum I do not have any issues with dissolving Salicylic acid in water. I used a mix of water\glycerin\propylene glycol\betaine\sodium citrate and some pH adjuster to dissolve it, but recently I found some old comment here, which claims that sodium citrate is actually neutralizes the acid instead of increasing it's solubility. Is this true? I remember some info from school's chemistry, that some strong acid can replace weaker acids in salts, but not sure I remember it correctly and it applies here.

Also, most of Korean brands use betaine salicylate in their products due to regulation laws. So I wonder if salicylic acid can react with betaine just in water or there should be some special reaction chains and I do not need to worry that SA in my formula is actually betaine salicylate?

Pharma

Mixing salicylic acid with betaine in water results in betaine salicylate (at a pH dependent degree).

Also, mixing salicylic acid with sodium citrate (mono-, di-, or tricitrate doesn't matter) results in sodium salicylate and citric acid (or a corresponding citrate). Again, the degree depends on pH and molar ratio.

In the end, all that matters is pH which turns salicylic acid into a more or less water soluble salt and thereby allows for easier dissolution. In low % aqueous or even anhydrous preparations wherein salicylic acid is soluble, production of salicylate salts results (for most cosmetic ingredients) in a reduced solubility.

Learntounlearn

Pharma said:

Mixing salicylic acid with betaine in water results in betaine salicylate (at a pH dependent degree).

Also, mixing salicylic acid with sodium citrate (mono-, di-, or tricitrate doesn't matter) results in sodium salicylate and citric acid (or a corresponding citrate). Again, the degree depends on pH and molar ratio.

In the end, all that matters is pH which turns salicylic acid into a more or less water soluble salt and thereby allows for easier dissolution. In low % aqueous or even anhydrous preparations wherein salicylic acid is soluble, production of salicylate salts results (for most cosmetic ingredients) in a reduced solubility.

Can you please elaborate on pH dependency when solvent used is water and betaine. How does Increase or decrease in pH alter the solubility. Does a pH range of 4-5.5 results in a stable solution. 

Pharma

When your solvent is water, solubility increases with increasing pH and can be estimated for any given pH using the pKa of salicylic acid (~3). At a pH of 4, 90% is in salt form and at a pH of 5, about 99% is in salt form. I don't know solubility of betaine salicylate (and less so the salt formed with whatever you use to set your pH) but assume that it's good enough. Hence, all you have to calculate is the corresponding amount of salicylic acid (in the example, 10% and 1%, respectively, of the added total amount). If that one is below the solubility limit of salicylic acid, you should be fine.

A factor which may influence solubility is the fact that betaine mixed with salicylic acid at the right proportion results in a liquid. I don't know how said liquid behaves in different solvents and to which degree it can be diluted with water before failing. Also, changing pH of this ominous liquid will change the required proportions, make it fail at one point, and alter tolerance to different solvents.

Hence, you should go with simple maths, for safety reasons stay below the theoretical limit, and simply try it out.

Bill_Toge

betaine forms a hydrogen-bonded complex with salicylic acid rather than a salt, which increases its solubility; I've formulated with it at pH 3.0-3.5, with a 2:1 molar ratio of betaine to acid and it remains relatively soluble (you still need some alcohol or DMI for maximum solubility)

toketsu

Pharma said:

Mixing salicylic acid with betaine in water results in betaine salicylate (at a pH dependent degree).

Also, mixing salicylic acid with sodium citrate (mono-, di-, or tricitrate doesn't matter) results in sodium salicylate and citric acid (or a corresponding citrate). Again, the degree depends on pH and molar ratio.

In the end, all that matters is pH which turns salicylic acid into a more or less water soluble salt and thereby allows for easier dissolution. In low % aqueous or even anhydrous preparations wherein salicylic acid is soluble, production of salicylate salts results (for most cosmetic ingredients) in a reduced solubility.

Does it mean that salicylic acid looses it's potency when dissolving it that way (because now it's not the acid, but salt)?

Pharma

It may. As said, all depends on the context... and your definition of 'potency'.

toketsu

Pharma said:

It may. As said, all depends on the context... and your definition of 'potency'.

I'll rephrase the question.
Imagine I have a solution of salicylic acid and sodium citrate in water with pH, e.g. 5.0. If I apply this on skin how it will work? As salicylic acid and sodium citrate would work, or as sodium salicylate and citric acid\sodium citrate would work?

All I want to understand if salicylic acid looses it properties when dissolving it that way.

Pharma

If you have a solution of salicylic acid at pH 5 (measured in the final product) it doesn't really matter what else is in there nor how you got to that pH, all that counts is the final pH. At a pH of 5, 99% of your salicylic acid will be in salt form and hence show less exfoliation, less deep skin penetration (which can be an advantage, you don't want SA in your bloodstream), but better tolerability. Skin antiinflammatory effect is likely still given (reduce swelling, redness etc.).

Citric acid will be present as sesquisodium citrate (~50% monosodium citrate and ~50% disodium citrate). It is unlikely to show much AHA/BHA effects.