Improving urea's stability in cream

Greetings,
I was wondering if anyone of you does have an idea regarding the improve of urea's stability in creams O/W which may contain an other active ingredient which makes the pH acid (around 3) of the cream.
The quantity of urea is 10%. Please note urea has low stability in the presence of water, high temperature and acid pH.

Thank you in advance

Comments

  • johnbjohnb Member
    A lactate buffer can help stabilise urea in solution but it is difficult to make an informed recommendation without knowing the identity of this other active ingredient and the other components of the cream.
  • Can you raise Ph to 4 as urea is most stable at 4--8.What is lowering the PH?
  • em88em88 Member
    Hello,
    Thank you for your replies. The other ingredient is salicylic acid.
    So with the current formulation, I adjusted the pH from around 3.5 to 5.5-6 with triethanolamine (2%). What I've noticed recently is that the pH after a few days will increase to 8-8.2. This worries me about the urea's stability. 
  • johnbjohnb Member
    What is the purpose of this cream?
    If it is as a keratolytic then it would most likely be better not to neutralise the acid with TEA.

    I worked on a urea/salicylic/lactic application for wart treatment and had no problems with stability. It contained 15% or so of propylene glycol and a fatty alcohol thickener.
  • em88em88 Member
    Indeed its purpose is to be keratolytic. 
    First formulations were without TEA, but after a few hours the cream had a "cheese" appearance due to CO2 release. 
    Did the cream you prepared remain at the same consistency? Also why did you add propylene glycol?
    Thank you
  • johnbjohnb Member
    The composition I worked on was more of a translucent gel rather than a cream. The propylene glycol was present to act as a solvent for the salicylic acid and as a humectant to prevent the gel drying out before it had chance to act. It also acted as a stabiliser for the whole product. There were no problems with consistency, possibly because it was not an emulsion in the commonly accepted meaning. My formulation also contained lactic acid as a salicylic acid stabiliser and as an auxiliary keratolyte.

    I don't understand why your composition should generate carbon dioxide. What are the ingredients?

    I don't understand either why you are neutralising the salicylic acid. It is the free acid that has the keratolytic properties, not its salts. From what we have been told, I think the whole concept needs reassessing.
  • em88em88 Member
    edited May 2017
    Your formulations seems to be far more better than mine, would you mind giving a few more details? Also what was the percentage of lactic acid and salicylic acid?

    I've read several articles claiming that urea decomposes with releasing CO2, especially in presence of water, acid pH (less than 4) and at higher temperatures. So I tried to avid all these incompatibilities. I agree with you regarding the concept of the formulation, that is why I am asking for help.
    Here is the current formulation
    Cetearyl Alcohol
    Petrolatum
    Paraffinum Liquidum
    Polysorbate 80
    Sorbitan oleate
    Cetyl palmitate
    Isopropyl myristate
    Triethanolamine
    Ethilic alcool
    Glycerin - 20%
    Salicylic acid
    Urea
    Purified water - 25%

    Thank you
  • em88em88 Member
    One more question, what was the pH of the gel?
  • johnbjohnb Member
    edited May 2017
    I worked on this more than 20 years ago and so any information is from memory and may be somewhat hazy.
    The product contained:

    Behenyl aclohol                             5
    Propylene glycol                          15
    Behenamidopropyl dimethylamine 4
    Lactic acid                                     6
    Salicylic acid                                10
    Urea                                              3
    Water to                                    100

    There were a few more ingredient but not any that woul make any difference to the overall product.

    I have no idea of the pH as any reading would be meaningless in the presence of so many interfering ions so it was not examined.
  • em88em88 Member
    edited May 2017
    The formulation you have worked was based more on the keratolytic effect, urea at 3% doesn't do anything extraordinary to the skin.:)
    I haven't considered a formulation for gel containing these two active ingredients, I would assume, if I get the same results of stability, the gel would be bubbly. In any case, I will try a formulation and see where it goes.  Thanks for the kind and help!

    Have a look at this patent. https://www.google.com/patents/WO2006102004A2?cl=en They do provide some formulations using NaOH. Also I have seen some other creams (last one was on amazon) containing TEA.
    Urea is such a pain to work with. I've noticed after unsealing the cream (from one of my earlier formulations) stored in tubes, the cream will get outside by itself proving an increase of pressure inside the tube which is caused most likely by CO2. 
  • johnbjohnb Member
    You are quite right that urea at 3% doesn't do anything. I doubt that higher levels do anything real, either. The reason that urea was included in my formulation was that my client insisted that it should be present. The final product did not contain urea and the only reason I gave the urea formulation here is because you requested that I do so.

    If you can get a suitable product without urea, I strongly encourage you to do so. If the main reason for the inclusion of urea is as a moisturiser rather than as a keratolyte then there are plenty of other materials which will fulfil that need (glycerine and propylene glycol even).

    In the link you have given, the NaOH containing examples are not of any particular importance, i.e they do not figure anywhere in the Claims.
  • em88em88 Member
    Unfortunately I can't remove urea and it has to be at 10% level. This ingredient is well known as "good" active ingredient for skin conditioning by patients that's why is highly requested. While salicylic acid should be at higher level (as you suggested at 10%), but for concentrations of over 2% the cream can only be registered as drug and not as cosmetic cream. 
    Was your salicylic acid gel transparent at the end or it got a whitish color? How did you manage to dissolve salicylic acid? 
    I'm sorry am asking you so many questions, but I'm kind of new in semisolid formulation, I've worked only with solid drugs.
  • johnbjohnb Member
    edited May 2017
    The gel was translucent (as stated previously) and contained microcrystals of salicylic acid. The acid was dissolved in the glycol (with heating) and the solution dumped quickly into cold water. There is more to it than stated there but the description gives an outline of the process.

    I am becoming a little confused. Are you formulating a cosmetic moisturiser or a fully functional keratolytic?

    The product I worked on was intended for the removal of warts and may not be applicable to what you seemingly want now.

  • em88em88 Member
    Hyperkeratosis dermatitis, follicular hyperkeratosis, ichthyosis, psoriasis, acne etc I'll need both the keratolytic and emollient effect. I know that the gel you prepared is for warts removal, I asked because I may have to make a gel formulation with 10% salicylic acid too and was curious how did you manage to dissolve the salicylic acid since 1g needs around 500g water to dissolve also you did not have alcohol in the formulation which would dissolve the acid much easier. I noticed now from my tests that the increase of pH was due to TEA acting very slow. I will try to find the ration of TEA and acid to maintain the pH within 4.5-8 were urea is stable.
  • johnbjohnb Member
    but for concentrations of over 2% the cream can only be registered as drug and not as cosmetic cream.
    The conditions you identify:
    Hyperkeratosis dermatitis, follicular hyperkeratosis, ichthyosis, psoriasis, acne etc

    are beyond the definition and capability of a cosmetic and any effective product should be classified as a drug.

  • chemicalmattchemicalmatt Member, Professional Chemist
    Two things here, friends: definitely apply the lactate buffer to his at pH 5.0 - plus, and add a lot of propylene glycol, not only to solvate SalAcid but to lower the water activity stabilizing urea even more.  Also: urea at 5.0% or more softens keratin (that would be skin, right?) remarkably well.  That is why it has been used in skin-softening creams for over 80 years. Urea is one the oldest known skin-care treatments in our industry.
  • Developed product similar to this with caveat it was anhydrous.Big seller. no sting from AHA.Consumers loved the product.
  • em88em88 Member
    johnb, I know, I have just mentioned where is the cosmetic going to be pointed. Obvious it will be described as a cosmetic. Thank you!
    chemicalmatt, I can add SalAcid up to 2% and reduce TEA to try to atchive pH 5 (I guess), can you please be more specific regarding the lactate buffer?
    I have added glycerin to lower the water, do you think propylene glycol would do better than glycerin?
    Unfortunately I'm not sure I can lower the urea to 5%. Thank you!
    DRBOB@VERDIENT.BIZ, did your product have urea? Thank you!
  • em88em88 Member
    Is it reasonable to think that starting from a formulation with 1% SA and 1.25% TEA, the pH increased from 5.5 to 7.9-8 and remained at this level, that by making the following change, 1.5% SA and 1% TEA the pH should be around 6-7? Or can I go straight to 2% SA and 1% TEA and still have a pH over 5? 
  • johnbjohnb Member
    Neutralised salicylic acid does not act as a keratolytic so there is little point in using TEA (or any other base) to do this.

    TEA salicylate (trolamine salicylate) is used as a topical analgesic.
  • em88em88 Member
    Hello,
    I have to at last to increase the pH to at last 4.5...
    I found an other cream in the local market. They use urea 15%, lactic acid (not specified the % and salicylic acid as preservative (most likely 0.5%). None of the ingredient mentioned on the box should increase the pH, still the pH is 7.4
    Petrolatum, aqua, urea (15%), glycerin, plant extract, cetyl alcohol, plant etract, lanolin, glyceryl stearate, plant extract, paraffinum liquidum, lactic acid, salicylic acid. The ingredient are written from the highest % to the lowest. 
    Any thought?
  • johnbjohnb Member
    Doesn't this:
    I found an other cream in the local market. They use urea 15%, lactic acid (not specified the % and salicylic acid as preservative (most likely 0.5%).
    take us back to my first reply in this thread:

    A lactate buffer can help stabilise urea in solution
  • em88em88 Member
    Yes, I've red that and was going to try (it's a great idea), but currently I don't have LA to make the buffer and it will take some time till I receive it, can I use an other buffer? For example phosphate?
  • em88em88 Member
    Ignore my last question. I did a research and found out that the lactic buffer isn't very suitable, while the citric buffer has better ranges. 
  • johnbjohnb Member
    I believe it is the lactate ion that is more important here, not the pH value.
  • @em88 we did not use urea nor did we use any base 
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