[BathroomChemist]

Citric acid can be anhydrous or a monohydrate, and sodium citrate can be anhydrous, monobasic, dibasic, tribasic, all with different molecular weights that will affect your pH calculations. If you’re using anhydrous citric acid and tribasic sodium citrate, then you should be right at pH 5.35. Fyi, I use the Curtipot spreadsheet to get an accurate estimate of pH.

I’ve read that conditioners can have up to 5 w/w% citrate while shampoos are typically around 0.1-0.5 w/w%. So you seem to be pretty high at 2.6% for a shampoo. I don’t make shampoos though, so I’ll defer to someone else on whether or not this is appropriate for your formula. You’re also at a buffer concentration of 100 mM, which seems pretty high (though this depends on what you’re adding). Do you need that much buffering capacity in your shampoo, and does citrate serve any other purpose?

In my serums, I have to worry about hydrolysis (in my case, of esters), which is a pH sensitive reaction that is accelerated at higher temperatures. If your formula is acidic or basic at your 70C step (basic is normally worse), then hydrolysis might be a problem especially when heating for longer times. In that case, adding a buffer before that step might actually be helpful. At the same time, citrate is a chelator, and if you have metals in your formula you might have a higher chance to get color changes if you have it in there at 70C. Generally, I think the buffer is added at the end, but again I’ll defer to someone who makes shampoos since I only make facial serums.

[BathroomChemist]

I make self-microemulsifying O/W microemulsions, but I haven’t tried making W/O/W emusions yet. However, from what little I’ve read, their formation requires a threshold shear force (which you can calculate). It sounds like you need to rupture the droplet in the second emulsification step, usually via high pressure homogenation. It sounds like you’re trying to supply this force via shaking? Some newer methods describe requiring lower shear forces in the second emulsification step. It’d be neat if you could build a device to supply this shear force into your bottle, though it’d probably require some innovation and experimentation and would drastically increase your packaging costs. Are you following the methods in any particular publication?

[BathroomChemist]

Can you also tell me about the material of the container, whether it’s glass or plastic, and if plastic what type? Since you said it’s a jar, I’m assuming that it’s glass.

[BathroomChemist]

So I scanned the entire 900 page handbook of excipient and looked at papers as far back as the 1950’s (which unsurprisingly used mercury containing compounds and dioxane because it’s the 1950’s) and I compiled a list of potential preservatives to use or not to use with non-ionic surfactants. Hopefully this will be helpful to others in the future:

Compatible: Sorbic acid, hexylene glycol, Imidazolidinyl urea (and likely diazolidinyl urea), propylene glycol (needs > 15% for antimicrobial activity)
Likely compatible: DMDM Hydratoin (compatible with non-ionic surfactants according to Ataman chemicals but no concentration specified)
Limited compatibility: Silver citrate (up to 2% surfactant), benzoic acid (antimicrobial activity partially reduced), benzalkonium chloride (incompatible at higher surfactant concentrations), chlorhexidine (incompatible at higher surfactant concentrations)
Incompatible: All parabens (10% propylene glycol protects against Polysorbate 80), phenoxyethanol, cetrimide, Chlorocresol, Chloroxylenol, m-Cresol

A paper from 1957 showed excellent activity against modern test organisms with 0.2% sorbic acid, 3% hexylene glycol, and a combination of these two. Note that surfactant concentrations rarely go above 5% in these tests. Also note that the list above is not authoritative and not quantitative for the most part (e.g. sources may not clarify what “higher surfactant concentrations” means). It’s just a compilation of what I found with a cursory literature review.

[BathroomChemist]

Thanks Phil, I’ll add that I do preserve the formula, just not with the typical parabens, phenoxyethanol…etc. I systematically tested the impact of each antimicrobial component with 9 separate screenings with pooled microbiota.

[BathroomChemist]

Thanks Matt, that’s extremely useful information. I heard from a couple researchers that things get a little weird when you hit 40C for microemulsions, particularly those with ethoxylated surfactants and the types of oils that I’m using. However, I have managed to keep the formula stable at 40C for 1 month so far with some slight tweaks. I doubt it’ll be stable for 3 months.

What I ultimately want is the ability to put an expiration date on the product and not wait an entire year to do this. Maybe I can consider longer tests at 30 or 35C? If it lasts for 1 month at 40C, can you say that it has an expiration date of 3-4 months? (I forget the actual conversion). I know that it undergoes a change around 40C, but I’d still feel comfortable with such a label because I know it will be a conservative estimate.

[BathroomChemist]

We’ll be repeating the PCPC with the modified formula using the R&D batch that the manufacturer will make this week. While I can formulate at home, we’re planning to have all official tests conducted using product made by an independent manufacturer. This way we’ll have a paper trail from the manufacturer to the testing facility with a record of ingredients and percentages from an independent party.

[BathroomChemist]

PCPC stands for Personal Care Products Council. The PCPC test is the most difficult PET to pass. It uses 10 times the number of bacteria as the ISO 11930 and USP<51>, similar concentrations of other organisms, and has more difficult passing criteria (e.g. greater log reduction after 7 days).

[BathroomChemist]

Nanocarriers can be tricky, but my grad school and postdoctoral research was in nanotechnology and I specialized in multifunctional and multilayered nanoparticles made from all sorts of materials. I can make microemulsions, lipsomes, and lipid nanoparticles at my home and do some preliminary characterization at local universities. In fact, I’m literally taking a day trip to my alma mater tomorrow to use a few tools in their characterization labs. We’ve got a team member who’s a professor and specialist in dermal drug delivery, and another good friend specializes in wearables.

[BathroomChemist]

Thanks for letting me know about Vitamin E phosphate. I wasn’t aware that it penetrated that deeply into the skin, but I suppose that makes sense because it’s water soluble. In my formula, I’m using nanocarriers to transport oil-soluble compounds deeply into the skin.

[BathroomChemist]

In typical formulation, I absolutely agree. However, I designed our delivery system to penetrate very deeply into the skin where Vitamin E acetate has a high rate of conversion.

[BathroomChemist]

I know that Vitamin E is effective against peroxyl radicals, singlet oxygen radicals, and lipid peroxide radicals, which oxidize oils through various mechanisms and stages. When the phenolic hydrogen on Vitamin E is replaced by acetate, it may very well not work as an antioxidant in the bottle.

[BathroomChemist]

I may end up taking the Vitamin C down a bit because it does seem a little high to me as well. I’ve read some publications about the therapeutic benefits of C and E, and believe that the combination of our delivery vehicle and approach of stabilizing the C will help, but I don’t think it will be that productive to debate the therapeutic benefits. From a marketing standpoint then, what percentages of Vitamin E do you typically see in creams, lotions, and serums that use it to slow the degradation of oils versus products that claim a benefit beyond stabilizing the oil phase?

[BathroomChemist]

While I can’t do very much about the high levels of non-ionic surfactant in my product, you do bring up an excellent point about ocular irritation by sweating. Looking at CIR, I see a lot about PEG-35 castor oil being a non-irritant to rabbit eyes at 13.5% but not much about PEG-40. Polysorbate 80 seems to be used as a lubricant in eye drops at 0.5%, and injection of 0.4% by syringe directly into the eyes of rabbits showed no irritation. However, I don’t see much about using 10%.

[BathroomChemist]

Does passing the ISO 11930 criteria A mean the product is also recognized as safe in US markets? In other words, does passing ISO 11930 criteria A make USP<51> unnecessary?

[BathroomChemist]

Thanks for sharing. What were the main preservatives if you don’t mind me asking?

[BathroomChemist]

Thanks for your input. I wasn’t sure when it became available because another article said that phyteq raspberry i multifunctional was set to debut at In-cosmetics Global in March.

My product is a serum, and the raspberry odor might be acceptable if it’s mild. I just took a look at its molecular structure, and I’m worried about that phenolic hydrogen that, if I recall correctly, reacts with non-ionic surfactants in parabens to inactivate them. Since I’m using non-ionics at high concentrations, it might be a poor choice for my system.

[BathroomChemist]

Sure, here you go: https://www.iq.usp.br/gutz/Curtipot_.html

I also settled on a citric acid buffer made with less than 0.5% citrate + citric acid

iq.usp.br

pH Calculation and Acid-Base Titration Curves - CurTipot Freeware for Data Analysis and Simulation

pH Calculation and Acid-Base Titration Curves - CurTipot Freeware for Data Analysis and Simulation

[BathroomChemist]

pH is right at 5.5 and the non-ionic surfactant is primarily polysorbate 80.

I did a bunch more digging to see if I might have missed some preservatives that could work with high levels of this surfactant, understanding that no negative interactions could simply mean not studied. I also found 1,2-Hexanediol and Sodium Dehydroacetate. I can’t find a good source of IPBC for testing that doesn’t come in a bucket.

It’d be nice to find an organic acid that won’t act as a nice carbon source for microorganisms. Maybe an aromatic?

[BathroomChemist]

Thanks Phil, the packaging is airless pump bottle, and while the formula is proprietary, I’ll say that it’s 25% oil phase, 14% non-ionic surfactant, and the remainder water phase. It’s not a typical product, so don’t be alarmed by the high surfactant concentration. No foaming, rubs in quickly, and feels very good on skin according to myself and a dozen other friends, family, and colleagues.

[BathroomChemist]

Fyi, I can screen 4 formulations for just $600. The plan as of right now is to try:

1) 1.5% caprylyl glycol EHG
2) 1.5% 1,2-hexanediol + caprylyl glycol
3) 1.5% caprylyl glycol + 1% phenoxyethanol (just to try it out)
4) 1.5% caprylyl glycol EHG + 3% hexylene glycol (if my formula can take it)

[BathroomChemist]

What are your thoughts on this article on Caprylyl Glycol and EHG? https://www.thaiscience.info/journals/Article/JHRE/10893376.pdf

I’d have no problem using parabens, phenoxyethanol, or quats, but they’re reported in multiple studies to be incompatible with non-ionic surfactants, especially at the concentrations I’m using. I considered citric acid, but it’s more likely to promote bacterial growth at pH 5. I tried hexylene glycol at 10% but it caused issues with the formula. I prefer not to use DMDMH due to regulatory concerns. I’m almost certainly going to do a cheaper antimicrobial screening before I pay for the full test, and penetration testing can be done for relatively cheap with the base formula. I’ll do the RIPT test only after everything is sorted out.

thaiscience.info

The resource cannot be found.

The resource cannot be found.

[BathroomChemist]

Thanks, I ended up buying both the citric and lactic acid and their conjugate bases and I’ll give both a try. I was personally more interested in lactic acid for some of the reasons you mentioned. Still a little worried about the pKa of lactic acid being 1.7 pH units from my target pH, but I may not need super good buffering capacity.

[BathroomChemist]

Still trying to get used to the terminology in this business (e.g. actives, excipients). I’d like to make a functional and general purpose serum, which will be used primarily for the face. I understand that no product will do everything, but I’d like to select ingredients that have multiple benefits for all skin types.

For vitamin C, I read about wound healing, collagen regeneration, reduced damage from the sun, and evening out skin tone for all skin types. For Vitamin B5, I read about improving skin elasticity, reducing inflammation, reducing redness from various skin conditions, and helping all skin types retain moisture. For Vitamin E, I read about its synergistic effects when combined with Vitamin C and soothing effects for all skin types. However, I’m very open to substitutions.

Basically, this will be a general purpose “hero product” in a line that will be expanded in the future to target specific functions.

[BathroomChemist]

Hi Phil (and others), I just wanted to give some updates on preservatives, especially since I had success, at least so far, with one of your recommendations. I purchased Hexylene Glycol to use at 10% based on published work showing broad anti-microbial activity at this percentage and compatibility with non-ionic surfactants, as well as DMDMH, silver citrate (despite manufacturer warnings), and a 3:1 mix of Caprylyl Glycol (CG) and Ethylhexylglycerin (EHG).

The Hexylene Glycol ruined my microemulsion. The silver citrate slowly precipitated out despite a pH of 5.5, which is in range. DMDMH at 2% and CG/EHG at 2% worked very well, at least in terms of preserving the microemulsion. I used double the recommended amounts of each to look for instability. I excluded every other common preservative (e.g. parabens, phenoxyethanol, benzoic acid, sorbic acid) because none of them are compatible with non-ionic surfactants > 5%.