Preservative problem

Hi. I made a water-based mask solution. I encountered a problem in my formulation using Glycerin; Aqua; Sodium Levulinate; Sodium Anisate (Dermosoft 1388 Eco from Evonik). Crystals were observed. I have read articles online that to avoid crystallization, pH should be adjusted to 4.0 - 5.5. My final ph is 5. Here's my formulation

Water
Citric Acid
Allantoin
Glycerin
Algae extract
Saccharide Isomerate
Glycoproteins

Still awaiting response from the supplier. But should you have any suggestions or comments on how can I improve my formula, please let me know. Thank you very much.

Comments

  • PharmaPharma Member, Pharmacist
    Depends on many factors. Are you sure it's the 1388 crystallising and not allantoin or IDK?
    How much of what does your mask contain?

    The lower the pH, the better 1388 works but the less soluble it becomes. You could try and add more glycerol, raising pH would help with solubility but this would also make the microbes very happy.
  • NatliaNatlia Member
    I have a serum with the same ingredients and many more but did not experience this problem. At what time are you adding Dermosoft 1388 Eco?
    It should be added to the water base first so the Ph at adding time would be >Ph7. Basically, add it first, and then the rest of the ingredients. At the end adjust PH to lower then 5.5.
  • Since Allantoin has limited solubility in water (and there are no solubilizers or surfactants in your formula), those crystals might well be from Allantoin.

    Another option is that since Allantoin has amine groups (amide to be more precise), they could react with Citric acid or Levulinate-Anisinic acid (from Dermosoft 1388), forming an insoluble salt. Maybe you could try lowering the pH to 4.0 (to reduce activity of amides) or adding a solubilizer?   
  • PharmaPharma Member, Pharmacist
    The amid group in allantoin will not react under normal conditions, let alone with a carboxylic acid ;) .
  • Hi @Pharma, thanks for your comment! I'm curious, almost all nitrogens in the structure of allantoin are in a plane, and their free electrons (which are in p orbitals) can participate in a resonance, so yeah, they are less likely to react...but the pending NH2 has a free pair of electrons in an hybrid sp3 orbital, which even though is not as good as a sp2 to interact, is still a good nucleophile, mostly when the pH is not so low. Wouldn't it be possible that it could react with carbonyl groups in carboxylic acids? 

    Again, thank you for your reply, and for the opportunity to debate a bit :)
  • PharmaPharma Member, Pharmacist
    I wouldn't say it's all in plane because there's a stereocentre which can be inverted due to mesomeric effects. Amids show mesomeric stabilisation and have the equilibrium on the C=O double bond and C-N single bond (N in sp3) and not on the C-OH and C=N side (sp2) and the oxygen pulls on the nitrogen which reduces its nucleophilicity even further. I wouldn't say that sp2 or sp3 are more or less reactive, it all depends on the compound (aromaticity), reaction type and, especially with nitrogen compounds, also solvatation and hence the used solvent.
    The one nitrogen you refer to is part of a substituted carbamide. Although carbamides can be brought to react this usually requires a fair bit of energy input and won't happen in an aqueous solution at room temperature.
    The product of your proposition would be an imide-like compound (can't find anything similar on Sigma Aldrich). Reactivity of carboxylic acids is poor especially if not present in their protonated form (low pH) whereas carbamides have pKb around 14 which would allow for a reaction at low pH (something not possible with amines). But I guess that the urea part would hydrolyse first.
    Maybe let it react with an activated carboxylic acid or at least a methyl ester? :)
  • ketchitoketchito Member
    edited September 1
    @Pharma Thanks again for the discussion and the clarification...I don't know hoy I missed that sp3 carbon to start with, and the attractive inductive effect of the CO next to the NH2.  

    I always appretiate a good chemical analysis  :)
  • Thanks for your response. Our supplier recommended to add the Dermosoft 1388 in the water phase prior adding other ingredients. But still, I experience crystallization but not as big as the previous crystals. Any other options?
  • @zacchaeus In your formula, I don't see anything to solubilize your Allantoin. Glycerin might help you incorporate it into the mixture, but to keep it solubilized, you might need something. You can try with PEG-40 hydrogenated castor oil, some polysorbate, or something of the kind. 
  • PharmaPharma Member, Pharmacist
    Try increasing glycerol. It will help with the 1388 and maybe with allantoin.
    But then again, it all depends on how much of what you have in your product ;) .
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