[Laurannecarly]

Thanks! we are not really looking to dissolve it, rather to produce something similar to say the Ordinary Ascorbic acid suspension in silicon which is kind of gritty and therefore not dissolved. Yet we would prefer to use silicons and would want to thicken a silicon alternative (for instance).

[Laurannecarly]

Just not sure how to achieve that

[Laurannecarly]

Or alternatively, we could combine a silicon alternative (ecosilk) with Zemea.

” Due to the instability of Vit C when in contact with water, new strategies and also new formulations are being proposed for the dissolution of the active. Appropriate solvents such as glycol to form one phase, appropriate oil phase such as silicone oil or another oil with a light feel. The Vit C is soluble in polyol solvents, such as propylene glycol, butylene glycol, hexylene glycol, glycerin, polyethylene glycols, glycereth-7, glycereth-26, ethoxydiglycol and ethanol. The advantages of using any of these solvents for nonaqueous emulsions are that they have less oxygen permeability and do not carry water, which prevent discoloration reactions in the formulation. These polyol solvents, appropriate oil phase and surfactants combined together, can form two immiscible phases which result in a nonaqueous or anhydrous emulsion that are heat-stable, non discoloring and also able to deliver the active.20“

[Laurannecarly]

Some food for thought:

https://knowledge.ulprospector.com/5286/pcc-anhydrous-oil-gellant-technology/

https://knowledge.ulprospector.com/388/pcc-diverse-technologies-polymeric-oil-thickeners/ 

[Laurannecarly]

I like your brainstorming

[Laurannecarly]

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.

[Laurannecarly]

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.

[Laurannecarly]

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…

[Laurannecarly]

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.

[Laurannecarly]

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?

[Laurannecarly]

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?

[Laurannecarly]

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!

[Laurannecarly]

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.

[Laurannecarly]

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.

[Laurannecarly]

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.

[Laurannecarly]

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.

[Laurannecarly]

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).

[Laurannecarly]

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?

[Laurannecarly]

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?

[Laurannecarly]

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.

[Laurannecarly]

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!

[Laurannecarly]

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.

[Laurannecarly]

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.

[Laurannecarly]

Dears,

Does anyone have any knowledge if it would be classified as patent infringement (of the CE Ferulic patent) when the formulation would be formulated at pH > 3.6? So the formula would contain 15% ascorbic acid, 1% vitamin E and 0.5% Ferulic acid at pH >3.6.

Also, I am currently using 1% Tocopherol (natural mixed tocopherol) to stabilise the AA. Is Alpha Tocopherol better for stabilisation purposes vs. natural mixed Tocopherols (that include Alpha Tocopherol as well, but at a lower concentration)?

Finally, what is the best pH adjuster when working with high concentrations of Ascorbic acid. I notice that the moment any pH adjuster is added, the degradation of AA occurs more quickly. Would Sodium hydroxide (20% solution) be a suitable option? Or would other pH adjusters be better to avoid negatively impacting AA stability?

Many thanks in advance!