Pressure build-up in 15% Ascorbic acid emulsion during stability testing

Dears,

We've been experiencing significant pressure build up/bubble formation after 2 weeks of 40 degree stability testing with an emulsion. There is minimal discolouration of the Ascorbic acid at this stage, so we are doubting whether this is related to the oxidation of the ascorbic acid. We cannot seem to solve the problem and would appreciate any thoughts.

The formula includes the following and is cold process.

Oil Phase:
- 2.5% Sepinov EMT 10 (Hydroxyethyl Acrylate/Sodium Acryloyldimethyl Taurate Copolymer)
- 1.2% Sucrose Stearate 
- 0.5% Sepiplus 400 (Polyacrylate-13 & Polyisobutene & Polysorbate 20)
- 5% Ecosilk (Isoamyl Laurate and Isoamyl Cocoate) --> to reduce stickiness of ascorbic acid
- 12% Sweet almond oil
- 1% Tocopherol 

Water Phase:
- 3.5% Dermosoft 1388 Eco
- 2% Sodium PCA
- 2% Glycerin
- 1% Panthenol
- 0.3% Sodium Phytate
- 0.1% Xanthan gum
- Water up to 100%

Post:
- 0.1% Ethylhexylglycerin
- 15% Ascorbic acid
- 5% Lactic acid
- 5% Sodium hydroxide solution (20% Sodium hydroxide solution)

Should point out that this is to have a 6 month expiry date from production as obviously the formula contains water and ascorbic acid. 

Would highly appreciate any thoughts.

Best regards

Comments

  • BelassiBelassi Member
    - 15% Ascorbic acid
    - 5% Lactic acid
    - 5% Sodium hydroxide solution 

    acid + base -> salt + water
    Cosmetic Brand Creation. Concept to name to IMPI search to logo and brand registration. In-house graphic design inc. Pantone specs. Cosmetic label and box design & graphics.
  • PerryPerry Administrator, Professional Chemist
    What's the beginning and ending pH?
  • BelassiBelassi Member
    I suppose I could do the stoichiometry, but that's your job as formulator. Perry's question gets directly there with an empirical method.
    Cosmetic Brand Creation. Concept to name to IMPI search to logo and brand registration. In-house graphic design inc. Pantone specs. Cosmetic label and box design & graphics.
  • PharmaPharma Member, Pharmacist
    ... We've been experiencing significant pressure build up/bubble formation after 2 weeks of 40 degree stability testing with an emulsion. There is minimal discolouration of the Ascorbic acid at this stage, so we are doubting whether this is related to the oxidation of the ascorbic acid...
    You can't necessarily correlate pressure/gas with discolouration. A gas takes a 1'000 times larger volume than a solid. In case of ascorbic acid, this would be hydrogen gas -> H2 is highly flammable and hence easy to test ;) . Though usually, ascorbic acid does not degrade like that but reacts with oxygen to form water or reduces other stuff = no bubbles and no pressure build-up but instead rather an underpressure.
    The main coloured degradation product of ascorbic acid is dehydroascorbic acid but it's not the only possible degradation product. It has just a beige colour and is therefore not always visibly recognized or only at higher concentrations. 0.1% degradation (of your 15%) will not be seen by the naked eye but could, in theory, produce a fair amount of pressure. Neglecting molecular weights, this would increase your product's volume by 15%. Similarly, a probably barely visible degradation of 1% of the added ascorbic acid would turn a 100 ml bottle into a 250 ml balloon.

    What does sometimes happen is degassing (liberation of air dissolved in water). Boiling your water before use helps against that. But that's purely speculative and I don't see anything which would stand out as a bubble-builder... true, knowing your product's pH might prove helpful.
  • PerryPerry Administrator, Professional Chemist
    edited March 3
    The type of packaging might matter too. What type of container are you using?

    I once worked on a VO5 Hairdressing problem  where some lots of tubes  (aluminum) were generating gas and bloating. The exact same formula put in a different tube didn't have the problem. I never did figure out what was causing it but it had something to do with the coating of the tube.  We changed tubes lots and the problem went away.
  • PharmaPharma Member, Pharmacist
    @Perry Aluminium (zinc and some alloys too) + acid = hydrogen gas. The effect may be stronger if antioxidants are present. The acid can be as simple and weak as diluted vinegar.
    Some tube coatings don't completely seal the whole inner surface or are susceptible to certain 'solvents', rendering them permeable enough for chemical reactions.
  • Perry said:
    What's the beginning and ending pH?
    Thank you for all the responses, we will take a good look!

    To respond to Perry's question, initial pH is 3.8, final pH is 3.5 after 4-week stability testing. Though this might be due to the fact that the Ascorbic acid has not properly dissolved yet immediately after production.

    Should point out that the pH of the water phase is very high (pH 9) due to the Sodium phytate.

    The material is glass. We use 15ml transparent glass samples to perform testing at this stage (brown borosilicate glass will be the final packaging).

    Please also find a picture of the sample with the white paper towel used as a colour reference. Note that most discolouration has occurred at the surface, there is less discolouration throughout the emulsion. There is approximately 15% expansion in volume after 4 weeks of stability which is very significant.


  • PharmaPharma Member, Pharmacist
    IMHO if your product was white in the beginning, that beige colour there means it's likely dead and doomed.
    BTW might be microbial contamination/fermentation too. This might also explain the drop in pH.
    Oh, and you shouldn't bottle and stabi-test something that's not yet dissolved to the point it should.
  • Pharma said:
    IMHO if your product was white in the beginning, that beige colour there means it's likely dead and doomed.
    BTW might be microbial contamination/fermentation too. This might also explain the drop in pH.
    Oh, and you shouldn't bottle and stabi-test something that's not yet dissolved to the point it should.
    Good point, will look into that. Btw the picture of the sample was 4-week stability, so the effects are more obvious vs the mentioned 2-weeks and demonstrate the issue better.
  • Hi All, I hope you are all doing well during these crazy times.

    We are still struggling with this formulation issue and cannot seem to solve it. Would love to get your thoughts on this. Here are the findings up until now based on further testing:

    - It does not seem to be related to the packaging in which the samples are stab tested
    - When the Ascorbic Acid is taken out, the problem is resolved, so it is related to the Ascorbic acid
    - The problem already arises without any discolouration of the AA happening, so we highly doubt it is just due to oxidisation.
    - We've also made sure the AA has been completely dissolved, so it does not seem to be related to that
    - We've tested with a Sodium hydroxide solution as well as Sodium citrate solution to adjust pH which also does not seem to impact it
    - We've tested with Phenoxyethanol/Ethylhexylglycerin as an alternative preservative, but actually it seems to make it slightly worse
    - We've tested with two forms of vitamin C, the crystallised form as well as the ultra fine powder form from DSM, both produce the same issue
    - Initial results show - this is not yet confirmed - when we increase the level of sucrose stearate, there seems to be more bubble formation, but it's not the whole problem as without it, it's still occurring

    Any thoughts would be much appreciated. 

    Have a good day!
  • PharmaPharma Member, Pharmacist
    Did you knock-out other ingredients such as tocopherol, lactic acid and most of the water phase?
    Assuming the issue is of chemical and not microbial nature, leaving preservatives and the like out might be okay for figuring out what's going to happen.
    Did you also use plastic packaging?
  • Thanks for your response. We did not leave out Tocopherol or lactic acid yet, do you think it could be interacting with the AA somehow?

    Will also test with knocking out the water phase ingredients. 

    Have not tested with plastic packaging yet. Only two different kinds of glass: clear glass jars and borosilicate amber glass vials.
  • PharmaPharma Member, Pharmacist
    Tocopherol is likely to interact with AA, lactic acid might... something has to, doesn't it?
    Hmm... glass should theoretically be as inert as plastic. Metal jars/tubes would have been my first guess (we've probably covered that already but I've forgotten it).
  • Haven't used any metal jars or tubes, so I guess that's not causing it. Tests are currently running.

    One more thing; I had a suggestion at some point that there might be traces of enzymes in the formula that could cause gas formation. Have you had any experience with that?
  • Bill_TogeBill_Toge Member, Professional Chemist
    was it aerated to start with?
    UK based formulation chemist. Strongest subjects: hair styling, hair bleaches, hair dyes (oxidative and non-oxidative) I know some stuff about: EU regulations, emulsions (O/W and W/O), toothpaste, mouthwash, shampoos, other toiletries
  • PharmaPharma Member, Pharmacist
    Enzymes are present as contaminants in/on most anything. But most do not produce gas, are not stable over time, are inactivated by heat (those which go into the product at 70°C will likely be destroyed), require specific conditions such as electrolytes and pH... some exceptions are enzymes found in laundry detergents which withstand harsh conditions and function under varied conditions but those do not produce gas. Common enzymes I recall which may result in formation of gas are (my brain is still halfway asleep) carbonic anhydratase and cytochromes. The former requires carbonate as educt though this will be gone if you bring your water to a rolling boil for a few minutes because by doing so, it degases (air, including oxygen and CO2 will 'evaporate') whereas cytochromes are sensitive to chelates such as phytate.
    Bottom line is: It's more likely that microbes are responsible.

    What I've noticed during my PhD is that oxidation (of ascorbyl palmitate but also certain additives used for enzymatic assays) is somewhat unpredictable. Simply changing a detergent/emulsifier or the buffer whilst maintaining the same pH and overall composition greatly impacts oxidation reactions. Also, presence of air (basically oxygen and CO2) in the medium is detrimental.
  • Thanks for you reply! You've been incredibly helpful.

    Very interesting. I should point out, we don't heat the formula whatsoever, it's cold-process. So perhaps that still opens up the enzyme option? Interestingly, there is only gas formation in the presence of Ascorbic Acid, so it must be that if there is enzymatic activity, it's mainly reacting with the AA.

    The reason I raise the enzyme option is also because of the phenomenon that the gas formation increases as we increase the sucrose stearate. And perhaps the sucrose acts as a source for the enzymes?

    Regarding your second point, are there any other emulsifiers you would recommend? Or in general, is there any additive that could enhance the stability of the AA (in an O/W emulsion) that we've not included?
  • Bill_Toge said:
    was it aerated to start with?
    Hi Bill! There is slight aeration at the start, but few very small bubbles. Then it seems new bubbles are formed building up significant pressure within a short period of stability testing. This is only the case with the AA contained, not excluding the AA (with exclusion of AA, there are also bubbles at the start, and no gas formation during stab).
  • PharmaPharma Member, Pharmacist
    Cold process, okay. Still, chances that you could blame enzymes is still very low whereas chances that it's microbial are higher.
    I'd try a test batch with boiled water. Simply boil it for a few minutes, fill it in a container up to the brim and close it as good as possible (to avoid contact with air), let cool and use that water directly without introducing too much air in the process. Hence, the final product shouldn't contain much oxygen. If you still have the very same effect (zero effect is unlikely, oxygen is everywhere)... then I'm like ??? Maybe try adding metabisulfite to quench oxygen?
    Sucrose stearate is a surfactant, it can speed up chemical reactions (lower surface tension equals better contact between molecules and it helps tocopherol to get in touch with AA*) and it also stabilises bubbles (instead of 'evaporating', gas gets trapped as visible bubble).
    *Tocopherol is known to act as oxidation booster under certain conditions and it regenerates AA if in contact with it (because one is in water, the other in oil, only an emulsifier brings them together). This means that one AA molecule might redox-cycle several times instead of being a one way ticket or, the other way round, it activates tocopherol better/more often so that tocopherol can do damage to whatever compound it does damage to. Given the respective % of the two, the latter option seems more likely but I can't see how tocopherol could produce gas.
    Unfortunately, the effect of emulsifiers on oxidation stability is not predictable, there is no good or bad, only trial and error will tell.
  • Pharma said:
    Cold process, okay. Still, chances that you could blame enzymes is still very low whereas chances that it's microbial are higher.
    I'd try a test batch with boiled water. Simply boil it for a few minutes, fill it in a container up to the brim and close it as good as possible (to avoid contact with air), let cool and use that water directly without introducing too much air in the process. Hence, the final product shouldn't contain much oxygen. If you still have the very same effect (zero effect is unlikely, oxygen is everywhere)... then I'm like ??? Maybe try adding metabisulfite to quench oxygen?
    Sucrose stearate is a surfactant, it can speed up chemical reactions (lower surface tension equals better contact between molecules and it helps tocopherol to get in touch with AA*) and it also stabilises bubbles (instead of 'evaporating', gas gets trapped as visible bubble).
    *Tocopherol is known to act as oxidation booster under certain conditions and it regenerates AA if in contact with it (because one is in water, the other in oil, only an emulsifier brings them together). This means that one AA molecule might redox-cycle several times instead of being a one way ticket or, the other way round, it activates tocopherol better/more often so that tocopherol can do damage to whatever compound it does damage to. Given the respective % of the two, the latter option seems more likely but I can't see how tocopherol could produce gas.
    Unfortunately, the effect of emulsifiers on oxidation stability is not predictable, there is no good or bad, only trial and error will tell.
    Thanks again for all your help. So we've done more testing, and it just seems that the gas formation is purely due to the oxidation of the Ascorbic Acid. There is one study where the anaerobic oxidation of AA is observed and this is exactly what we've been experiencing: https://www.tandfonline.com/doi/full/10.1080/10942912.2013.805770

    Perhaps it's due to the fact our product is an emulsion with a higher viscosity than 15% AA serums in the market (e.g. C E Ferulic by Skinceuticals, Paula's Choice C15 and C Firma by Drunk Elephant). We perhaps see anaerobic oxidation quicker (vs aerobic) as throughout the emulsion, there is limited direct contact with oxygen due to the higher viscosity.

    It does make us wonder though how these brands can achieve the 15% AA and have it be relatively stable for up to 3 years. Though I guess all of these serums have a yellow to orange colour which either indicates some oxidation and / or the use of ingredients to give an orange colour to cover up oxidation over time. Feedback on these products is very positive, although the metal-like smell indicating at least partial oxidation is not uncommon.

    I do have to point out that at lower temperature stability testing (32-35 degrees) when compared to the 45 degree samples for accelerated testing the lower temperate sample have significantly less pressure buildup (when corrected / converted to the same shelf life).

    We are now testing at lower concentrations to see if we can achieve an acceptable shelf life.
  • EVchemEVchem Member
    I  seriously doubt any of those products have  true stability for 3 years. 
    Also I believe C Firma is still being investigated for violating the skinceuticals patent  for C E Ferulic . https://www.vox.com/the-goods/2018/11/16/18098503/loreal-drunk-elephant-skinceuticals-lawsuit
  • EVchem said:
    I  seriously doubt any of those products have  true stability for 3 years. 
    Also I believe C Firma is still being investigated for violating the skinceuticals patent  for C E Ferulic . https://www.vox.com/the-goods/2018/11/16/18098503/loreal-drunk-elephant-skinceuticals-lawsuit
    Yeah you're probably right. As per your link - Skinceuticals its 'hot dog water serum' - is not what a freshly produced vitamin C serum smells like. Though it does not smell amazing either.

    Interestingly, we've also ran experiments with Ferulic acid just to try it and have not found it to make any difference.
  • BelassiBelassi Member
    I seriously doubt their formula lasts for three weeks, let alone three months. I was unable to get a vitamin C formula to exceed a genuine shelf life of three weeks, even though I was using a super-expensive Japanese derivative, adopted their recommendations, and packaged in an airless pump. In the end I gave up.
    Cosmetic Brand Creation. Concept to name to IMPI search to logo and brand registration. In-house graphic design inc. Pantone specs. Cosmetic label and box design & graphics.
  • Belassi said:
    I seriously doubt their formula lasts for three weeks, let alone three months. I was unable to get a vitamin C formula to exceed a genuine shelf life of three weeks, even though I was using a super-expensive Japanese derivative, adopted their recommendations, and packaged in an airless pump. In the end I gave up.
    I'm honestly quite happy to hear this, as the process has been very frustrating. We have been trying to achieve 6 months (we would communicate an expiry date). The concept is based on fresh batches produced each time, so that it can be as fresh as possible. But still not there... It's not the discolouration we're worried about (which is less than what CE Ferulic), but obviously the pressure buildup is the issue.
  • BelassiBelassi Member
    In my case I had no production of gas at all. It would have been very obvious in an airless pump. I was using this:
    Apprecier is a stabilized provitamin C formed from L-ascorbyl 2-phosphate (aqueous Vitamin C) and L-ascorbyl 6-palmitate (oil soluble Vitamin C), an amphipathic compound.
    It's terrifically expensive. Early results really impressed me. At 2% I was getting visible wrinkle reduction and skin tone lightening, after about 3 weeks use as a night cream. My first problem was selling price. The formulation was very expensive and the fancy airless pump, too. Then there was the box, the instruction pamphlet... 
    Then came the stability problem. At around 7-8 weeks, it began to turn brown. It ended up a latte sort of colour after about 10 weeks.
    Given the production and packaging cost, high selling price, and poor shelf life, I decided to cut my losses.
    Cosmetic Brand Creation. Concept to name to IMPI search to logo and brand registration. In-house graphic design inc. Pantone specs. Cosmetic label and box design & graphics.
  • Belassi said:
    In my case I had no production of gas at all. It would have been very obvious in an airless pump. I was using this:
    Apprecier is a stabilized provitamin C formed from L-ascorbyl 2-phosphate (aqueous Vitamin C) and L-ascorbyl 6-palmitate (oil soluble Vitamin C), an amphipathic compound.
    It's terrifically expensive. Early results really impressed me. At 2% I was getting visible wrinkle reduction and skin tone lightening, after about 3 weeks use as a night cream. My first problem was selling price. The formulation was very expensive and the fancy airless pump, too. Then there was the box, the instruction pamphlet... 
    Then came the stability problem. At around 7-8 weeks, it began to turn brown. It ended up a latte sort of colour after about 10 weeks.
    Given the production and packaging cost, high selling price, and poor shelf life, I decided to cut my losses.
    Sounds like an interesting derivative of Vit C though if it can achieve results at just 2%! Sometimes you just need to try things...

    We are also now looking into derivatives (probably MAP), but I personally just still can't seem to accept letting go of Ascorbic Acid completely.
  • We have used ascorbyl glucoside successfully in many formulations.It is unlikely you will get stability with Ascorbic acid:also Map discolors with time at 50C.AG penetrates skin and provides a slow release of VC. 
  • PharmaPharma Member, Pharmacist
    ...There is one study where the anaerobic oxidation of AA is observed and this is exactly what we've been experiencing: https://www.tandfonline.com/doi/full/10.1080/10942912.2013.805770...
    As long as you don't determine degradation products, there is no telling which way degradation runs. The anaerobic pathway releases CO2 in an early step. Aerobic degradation runs via dehydroacetic acid, a reaction which can be reverted using the right antioxidants, and only at a latter point releases CO2. And both pathways release H2. Bottom line: same amount of gas, just that anaerobic is a bit faster.
    Unfortunately, it's fairly difficult to get water content low enough to considerably slow things down without switching to an anhydrous formulation.
    Can't remember whether or not you told us the pH of your emulsion. According to your link, increasing pH towards neutral might help to slow degradation reactions down. Downside is, efficacy of your product might go down.

    Assuming you couldn't stop degradation but are just looking for a cover-up:
    Avoiding PCA might help because it's likely contributing to colour formation (publication). PCA might even speed up degradation by creating a 'sink condition' (removing reaction products and thereby turning an equilibrium into a one way street).
    Removing CO2 could be achieved by using an appropriate buffer system. I don't know if your lactate buffer works well for carbonate. Only looking at pKa, I'd go with citric acid. An amine instead of NaOH might hypothetically also work better. MEA (monoethanolamine) as a volatile base bears the ability of catching CO2 also in gas form; it's used industrially for this purpose. However, the very low pH greatly reduces volatility of MEA, not to speak of MEA probably not being the best cosmetic ingredient. DMEA on the other hand... it's less reactive and less volatile but a great cosmeceutical. It stinks less too but it still reeks of dead fish (you'd have to use free base DMEA and not the less smelly and more often used bitartrate salt).
    In theory, simply increasing pH would already help to turn carbonic acid into bicarbonate. Sadly, one problem with CO2 is that it doesn't readily convert to carbonic acid just by being dissolved in water. Our body uses carboanhydratase enzymes to speed up this process. Using ionic liquids or deep eutectic solvents instead of water would be another approach... but that's likely too sciency for a cosmetic product.
    Removing H2 could be attempted by adding an oxidised compound. Off the top of my head, suitable cosmetic ingredients might be alpha-lipoic acid and glutathione (cystine isn't commonly used), or certain synthetic dyes (which turn colourless upon reduction ;) ). These withstand direct reduction by ascorbic acid but should react with H2. However, this is just a guess... it works nicely with H2 in situ generated by mixing zinc powder with diluted acetic acid. The advantage would be that the created reduced compounds are strong antioxidants and will regenerate ascorbic acid from dehydroascorbic acid.
  • PharmaPharma Member, Pharmacist
    Back from a walk with the doggies and some time of thinking...
    There are a few flaws in my above post:
    - MEA would be your worst choice. It reacts colourful with ascorbic acid degradation products.
    - DMEA shouldn't be a problem because it is a tertiary amine. Unfortunately, there are a few exceptions which do degrade for example in the presence of ascorbic acid such as MES and MOPS which do so via not so healthy amine oxides. Like PCA shouldn't pose a problem but yet it does, such incompatibilities aren't predictable applying schoolbook chemistry laws. Whether or not DMEA is suitable or not, I do not know. From experience with MOPS, degradation is visible within hours to days. DMEA is known to scavenge hydroxyl radicals from ascorbic acid degradation (for example in presence of EDTA chelated iron)... Best would be some means to determine DMEA degradation in case you decide to go with that.
    - Lipoic acid won't work because it's oil soluble.
  • Pharma said:
    Back from a walk with the doggies and some time of thinking...
    There are a few flaws in my above post:
    - MEA would be your worst choice. It reacts colourful with ascorbic acid degradation products.
    - DMEA shouldn't be a problem because it is a tertiary amine. Unfortunately, there are a few exceptions which do degrade for example in the presence of ascorbic acid such as MES and MOPS which do so via not so healthy amine oxides. Like PCA shouldn't pose a problem but yet it does, such incompatibilities aren't predictable applying schoolbook chemistry laws. Whether or not DMEA is suitable or not, I do not know. From experience with MOPS, degradation is visible within hours to days. DMEA is known to scavenge hydroxyl radicals from ascorbic acid degradation (for example in presence of EDTA chelated iron)... Best would be some means to determine DMEA degradation in case you decide to go with that.
    - Lipoic acid won't work because it's oil soluble.
    Thanks so much for your time and thorough input. I need to look into this and digest this for a bit, but it seems like there are further some interesting tests to run. Will get back to you with an update. Thanks!
  • PharmaPharma Member, Pharmacist
    ...Will get back to you with an update. Thanks!
    You're welcome.
    Looking forward to hear how it goes.
  • Pharma said:
    ...Will get back to you with an update. Thanks!
    You're welcome.
    Looking forward to hear how it goes.
    By the way, do you have any thoughts about the lipoic acid concentration? Am considering 1-2% but not sure. Would you include in the oil phase (potentially with some flaxseed oil to dissolve it), or would you add it in post?
  • PharmaPharma Member, Pharmacist
    As said, lipoic acid is unlikely to help with stability of AA due to it being dissolved in the oil phase at low pH and assuming that it's not going to turn into dihydrolipoic acid it won't have any protective effect on the oil phase either.
    I would also only add more fancy ingredients after you've figured out a stable prototype.
    Once there, I'd dissolve lipoic acid in the oil phase.
    I certainly wouldn't add flaxseed oil. Given your stability issues, I'd even consider switching almond oil for a more stable one. Either MCT, jojoba or 'synthetic' ester oils or for a natural somewhat unsaturated fatty acid profile a seed/nut oil like meadowfoam, crambe, or macadamia.
    Since ester oils like coco caprylate are of low viscosity, highly spreading and 'drying', a combination with a refined seed butter could give a closer 'sensorial' match to almond oil whilst being more stable than a seed/nut oil. At least, check analysis protocols for your oil; only use batches with a low peroxide value.
    Reason why I mention oil stability is that tocopherol may act as pro-oxidant at higher %. Literature data are not conclusive but 1% as antioxidant seems a lot and that for maybe not too much of an effect on skin. Degrading tocopherol also drives degradation of ascorbic acid which regenerates tocopherol until there is nothing left for toco to degrade. Thereby formed dehydroascorbic acid may even speed up oxidation processes... Lipid peroxidation & degradation can also release CO2, not just self-degradation of AA. Hence, it's unknown what exactly degrades to an unknown gas apart from AA being somehow involved. Therefore, it seems wise to do anything to increase stability of the whole formulation even if you're just after AA.
  • Pharma said:
    As said, lipoic acid is unlikely to help with stability of AA due to it being dissolved in the oil phase at low pH and assuming that it's not going to turn into dihydrolipoic acid it won't have any protective effect on the oil phase either.
    I would also only add more fancy ingredients after you've figured out a stable prototype.
    Once there, I'd dissolve lipoic acid in the oil phase.
    I certainly wouldn't add flaxseed oil. Given your stability issues, I'd even consider switching almond oil for a more stable one. Either MCT, jojoba or 'synthetic' ester oils or for a natural somewhat unsaturated fatty acid profile a seed/nut oil like meadowfoam, crambe, or macadamia.
    Since ester oils like coco caprylate are of low viscosity, highly spreading and 'drying', a combination with a refined seed butter could give a closer 'sensorial' match to almond oil whilst being more stable than a seed/nut oil. At least, check analysis protocols for your oil; only use batches with a low peroxide value.
    Reason why I mention oil stability is that tocopherol may act as pro-oxidant at higher %. Literature data are not conclusive but 1% as antioxidant seems a lot and that for maybe not too much of an effect on skin. Degrading tocopherol also drives degradation of ascorbic acid which regenerates tocopherol until there is nothing left for toco to degrade. Thereby formed dehydroascorbic acid may even speed up oxidation processes... Lipid peroxidation & degradation can also release CO2, not just self-degradation of AA. Hence, it's unknown what exactly degrades to an unknown gas apart from AA being somehow involved. Therefore, it seems wise to do anything to increase stability of the whole formulation even if you're just after AA.
    Thank you! Makes sense.

    One of the samples we had created included Resveratrol, which is a rather impossible combination but just an interesting experiment. Yet when comparing a sample with and without the Resveratrol there is barely any pressure buildup in the Resveratrol sample. There is aerobic oxidation occurring though. It seems to be the Ascorbic Acid is primarily / initially oxidising as the emulsion slowly turns yellow, before turning into a latte like colour on stability. (Whereas we found Resveratrol just turns into a latte like colour when oxidising.)

    Though this is quite interesting as there is no gas formation which is what we're after. Yet the issue is that the Resveratrol sample separates after 5 days at 45 degrees... We can repeat this sample along with variations of your other instructions (including the use of a more stable oil, citric acid, removing PCA, removing vit E) just to see how Resveratrol impacts it. What do you think?
  • PharmaPharma Member, Pharmacist
    Resveratrol is a phenolic compound and behaves similar to tocopherol but it has a certain water solubility which tocopherol is lacking. Resveratrol is also better regarding protecting lipids from peroxidation and is slightly superior in several antioxidant tests.
    Its solubility in water and oil allows it to shuttle between ascorbic acid (water phase) and lipids (oil phase). As an educated guess, this would mean that resveratrol pushes degradation pathway towards the aerobic side. Maybe, there is no CO2 formation (if it is CO2 and not H2 -> hold a burning match to a larger bubble ;) ) because aerobic degradation doesn't go all the way down to the step of CO2 formation?
    Unfortunately, this amphiphilic character also allows it to interact with certain emulsifiers which might explain the observed stability issues.
    BTW colour reactions such as seen with ascorbic acid degradation are not correlated with actual % of degradation and won't tell you whether it's aerobic, anaerobic, or mixed type degradation.

    Do you have means of running experiments like simple chemistry tests such as determining peroxide value or ascorbic acid quantification (you'll need iodide or iodine, respectively, and some other basic chemicals), run a TLC, or even got fancy machines?
  • Very interesting! Just created new samples with Resveratrol as well as your other tips to enhance stability, also knocking out the vit E. Hope that will help avoid / delay separation. Would it be worth increasing the Sepiplus 400 (Polyacrylate-13 & Polyisobutene & Polysorbate 20) or any of the other (co-) emulsifiers (Sepinov EMT 10 or Sucrose Stearate)?

    It seems you are most probably right about the CO2, as when I test a vial with pressure buildup / bubbles, it immediately extinguishes the flame (no pop). 

    It would indeed be good to get a better understanding of what oxidation is occurring as well as understanding residual unoxidised Ascorbic Acid at the end of stability, will look into this.
  • If it's true the Resveratrol really helps avoid the CO2, I'm wondering whether to lower the pH back from pH 4.1-4.3 to 3.5-3.8 again as according to some studies AA does appear to be more stable at lower pH. Unfortunately when including Lactic acid I can't go below pH 3.5...
  • If it's true the Resveratrol really helps avoid the CO2, I'm wondering whether to lower the pH back from pH 4.1-4.3 to 3.5-3.8 again as according to some studies AA does appear to be more stable at lower pH. Unfortunately when including Lactic acid I can't go below pH 3.5...
    Considering to replace Lactic acid with Salicylic acid - if we can incorporate that without any of the typical Salicylic acid solubility issues which would cause more trouble - to be able to lower the pH to 3.2-3.5. We would also need less NaOH which does seem to impact stability when increased according to test results. But would need to test if indeed that makes a difference vs. the Lactic acid at higher pH.
  • PharmaPharma Member, Pharmacist
    edited May 13
    Unfortunately when including Lactic acid I can't go below pH 3.5...
    Why? Doesn't make any sense to me... Is lactic acid getting dangerous below 3.5?
    Salicylic acid won't be a good replacement because, unlike lactic acid, free salicylic acid is not water soluble.
    From what I've read, at a pH between 4.4 and 5.6, self-degradation of ascorbic acid is slowest. Anything you add which increases solubility (some solvents and free lactic acid might likely be considered one) increases speed of degradation. Other publications indicate that pH doesn't matter regarding for example lipid peroxidation by AA degradation products (obviously not by AA itself which prevents it).
    Furthermore: anaerobic degradation is favoured by low pH whereas aerobic degradation depends on AA deprotonation (which happens in alkaline conditions and requires oxygen).
    Bottom line is: You shouldn't lower pH and it certainly doesn't mean you should do so by adding another acid but if really necessary, just use less sodium hydroxide. Quite the opposite, you should increase pH to +/- 5 and avoid oxygen. Because iron and copper have a tremendous effect on degradation speed especially at the most stable pH range, it also means you should avoid trace metals in your ingredients (most likely source in your case is almond oil and technical grade sodium hydroxide) and use a good chelate appropriate for the formulation's pH.
  • Right! Ok makes sense! The Lactic acid below 3.5 I understood what the lowest as permitted by regulation for AHAs (BHA is lower I believe). But if this doesn't make sense to lower it further then it doesn't matter. The only thing is that by increasing it between 4.4 and 5.6, the exfoliating effects of Lactic acid are probably not happening, but then again stabilising the AA is of highest priority.
  • PharmaPharma Member, Pharmacist
    edited May 14
    I don't know if it works (I don't even know if my brain still works, 't was a looong day) but what if you included triethyl citrate in your formulation? It's supposed to degrade to citric acid and thereby lower skin pH, faster where bacteria grow but it's also metabolised in living skin cells. Might be a trick to make 'high' pH lactic acid work better. Again, just brainstorming here!
  • I like your brainstorming :)
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