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Pressure build-up in 15% Ascorbic acid emulsion during stability testing
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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.
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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.
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Laurannecarly said:…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. -
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.
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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!
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Laurannecarly said:…Will get back to you with an update. Thanks!You’re welcome.Looking forward to hear how it goes.
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Pharma said:Laurannecarly 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?
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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.
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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?
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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?
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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.
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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…
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Laurannecarly said: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.
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Laurannecarly said: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.
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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.
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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!
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I like your brainstorming
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