[XYZ123]

I have the same question. Were you able to figure it out?

[XYZ123]

Hello Perry,

In this case, do you think it is okay to go straight to freeze thaw testing and incubator testing directly to do the stability testing and it still should be fine?

[XYZ123]

Hello. Sorry. I rechecked the info. Aculyn 33 is anionic.

Aculyn™ 33 rheology modifier is an alkali-swellable anionic acrylic polymer emulsion (ASE) that is lightly cross linked to impart a short pseudoplastic flow. It is a liquid, cold-processable product that instantaneously thickens upon neutralization providing ease of handling and increased manufacturing efficiency. This thickener is offered at 28% solids and is compatible with peroxide and other oxidizing agents, electrolytes, polar solvents and zinc pyrithione. The polymer has a well-established toxicological profile and is safe in normal use

[XYZ123]

Hi chemicalmatt,

When you said none of the above, do you include Aculyn 33 as well in the non-electrolyte resistant materials? I read the brochure of Aculyn 33 and it says it has a good electrolyte resistance feature because of its non-ionic nature. I just want to confirm if it is true because sometimes supplier data does not always work on real-life applications.

Also, for o/w emulsions with high electrolyte content (around 2-5% NaCl), what’s your best pick of cold processable polymeric emulsifiers? I’ll be glad to hear back from you.

thank you in advance.

[XYZ123]

Hi Sarah, I plan to buy Aculyn 33 as well. Do you somehow know a raw material supplier than can sell this material at a lower MOQ? Also, is it true that Aculyn 33 is non-tacky and has a good skin feel based from your experience?

[XYZ123]

Slr. I see. thank you so much. I have another question though.

I have hydroxypropyl starch phosphate as well. I bought it from Myskinrecipes in Thailand. As far as I know, it is not necessary to alkalize it or acidify it for it to swell and build its internal network. But when I put it in water and mix it using low-medium shear, it still won’t gel. also, after stopping the mixing, after an hour, there will be like some sort of a phase separation - like the starch is separating from water. I only put 0.1% w/w NaCl to water to test its electrolyte resistance. Would you mind telling me if I am doing something wrong?

Process:

Water - q.s.

NaCl - 0.1 w/w

Hydroxypropyl Starch Phosphate - 4% w/w

>> Dissolve NaCl in water then add Hydroxypropyl Starch Phosphate. Mix for 15-30 mins under low-medium shear.

Low shear mixing paddle - viscojet

Medium shear mixing paddle: rotosolver

[XYZ123]

what do you mean by that? aristoflex avc is better compared to structure xl when it comes to overall skin feel?

[XYZ123]

By the way. the application is for cosmetics.

[XYZ123]

Do you by any chance know how much is typically needed to create a stable microemulsion of 5% of safflower oil in the water continuous phase?

oil - 5 grams

water - 60 grams

surfactant required for microemulsion?

thanks in advance

[XYZ123]

Thanks Phil. 🙂

[XYZ123]

Hello Phil. I have another question. EDTA is known to be a preservative potentiator. Can I replace it with Sodium Phytate and still be a good preservative potentiator? Or EDTA is still the gold standard?

[XYZ123]

Additionally, I hadn’t really thought of exploring injectables in depth. However, after you mentioned it, I realized they also utilize preservatives to maintain their stability. This strongly suggests that their preservative systems are highly likely robust enough to control microbiological contamination while also being biocompatible with the human body.

This is another scope of preservation that is quite interesting for me as well. I will await further communication from you regarding that another person you have in mind.

Also, if you have more tips for me about things that you have learned from your experiences in the field, I would love to know more about it.

[XYZ123]

Thank you so much, Dr. Geis, for your input. I totally agree with you. Even after reading a lot of resources and digging into published studies in Google Scholar and other resources, I still couldn’t find much information that can give me a high degree of confidence that what I am formulating has low levels of toxicity while maintaining the highest quality of microbiological control. I also had this gut feeling that something doesn’t add up right, especially that everybody is claiming to be effective even if I have heard that some of my coformulators had seen failed PET with those marketed materials that claim to be broad spectrum.

Yes! I would love to work with that someone that you are referring to as well, just the same way I’d love to collaborate with you. Can you please hook me with that person?

Thank you again, Dr. Geis. I couldn’t thank you enough for your guidance.

I will remain attentive to your response.

[XYZ123]

Hello Phil, thank you so much. I am immensely grateful for your help. I also sent him an email already. Many thanks. 😃

[XYZ123]

Got it. Phil. Thank you.

I will wait for your updates.

[XYZ123]

😮 Wow, thank you so much, Dr. Geis. It’s a pleasure to be able to talk to you in this forum.

Let me tell you more about my formula and the help I need. Also, please feel free to correct me if any part of my understanding is off.

I’m working with chemical actives that need to bypass the stratum corneum to be effective. To do this, I use a permeation enhancer like bis-ethoxydiglycol-cyclohexane 1,4 dicarboxylate combined with osmolytes to help these actives penetrate the skin. However, the challenge is that permeation enhancers don’t just selectively increase the bioavailability of the active ingredients—they also enhance the absorption of all the ingredients in the formula.

In general, chemicals with a molecular weight under 500 daltons can permeate the skin more easily when permeation enhancers are used - assuming there aren’t any structural issues with the molecules. So, by increasing the bioavailability of the active ingredients, I’m also increasing the bioavailability of preservatives, which are typically under 500 daltons in size. If I increase the bioavailability of preservatives, I could face potential safety concerns related to toxicity.

I’m currently looking for a broad-spectrum preservative that would be biocompatible with humans, even if absorbed systemically, or at least non-toxic. My formulation is a cream/lotion with a final pH range of 3.8–5.5 (including any pH drift), with the final pH around 4.5–4.7.

I’ve read various brochures from different manufacturers, information sheets, and modules from the cosmetic formulation course I’ve taken at the Institute where I study cosmetic chemistry. I’ve also reviewed the book you are the chief editor of, Cosmetic Microbiology: A Practical Approach (third edition), though I haven’t finished it yet. In my search for an effective preservative system with minimal toxicity, I’ve come across the following information:

1. Sorbates, Benzoates, and derivatives are used in food preservation, often alongside other preservation methods like QACs, refrigeration, and water availability manipulation. From this, I concluded that since these are food-grade ingredients, systemic absorption is unlikely to cause toxicity in humans. Of course, I’ll still follow regulatory limits for all cosmetic ingredients.

2. Dehydroacetic Acid is allowed in oral care products, according to the Geogard 111A brochure [INCI Name: Dehydroacetic Acid], with a recommended use level of 0.1–0.6% w/w.

3. Organic Acids are effective against Gram-positive bacteria, yeast, and molds but have limited efficacy against Gram-negative bacteria (which are more common in water-based systems). To address Gram-negative bacteria, organic acids are often paired with other preservatives like phenoxyethanol, MCIT, or formaldehyde releasers.

4. Chelators can improve the efficacy of preservatives.

5. Ethylhexylglycerin enhances the effectiveness of phenoxyethanol.

6. It’s ideal to have a pKa value that is less than or equal the pKa value of organic acids in order for it to perform at its best:

   • Benzoic acid: pKa 4.2
   • Dehydroacetic acid: pKa 5.26
   • Sorbic acid: pKa 4.76
   • Sodium dehydroacetate: pKa 5.36
   • Potassium sorbate: pKa 4.69
   • Sodium benzoate: pKa 4.08

Hurdles:<div>

1. Euxyl K712 contains potassium sorbate, sodium benzoate, and water.

   I’d prefer to use it as an antifungal and antibacterial agent against Gram-positive bacteria. According to your book, it works best when paired with phenoxyethanol, methylchloroisothiazolinone (MIT), or formaldehyde releasers. However, I can’t use MIT because of its sensitization issues in leave-on products, and I can’t use formaldehyde releasers due to the potential risk of increasing formaldehyde bioavailability, which could raise concerns about carcinogen exposure. As far as I know, as long as it’s used within regulatory limits, formaldehyde releasers are considered safe, but because permeation enhancers increase bioavailability, I don’t want to take the risk.

2. Sorbic acid is also food-grade but can degrade in the presence of glycerol and some salts, which are in my formula. So, I can’t use sorbic acid either.

Other preservatives that can be used around the mouth:

Sepicide G - made up of Glycerin and Ethyl Laurol Arginate > the problem with this is that efficacy is reduced by the presence of anionic ingredients.

TroyCare EPP37 - made up of ethylhexylglycerin + phenylpropanol > I don’t know much about the bactiricidal/bacteristatic or fungicidal/static efficacy of phenylpropanol. I also don’t know if it is effective against gram + and/or - bacteria?

Geogard Ultra - made of gluconolactone, sodium benzoate > not sure if this is still safe when the bioavailability is increased by permeation enhancers. Not also sure if it is effective against gram + and/or - bacteria?

Final Verdict:</div><div>

For a robust preservative system in my case, I’m considering:
Euxyl K712 + phenoxyethanol + ethylhexylglycerin + chelator. This combination should effectively target Gram-positive and Gram-negative bacteria, yeast, and mold. But I want to confirm whether this system would still be non-toxic when bioavailability is increased? Is my understanding of this combination correct?

My logic is that if these ingredients can be safely used in oral care products, they should have a low toxicity profile for humans, especially when used within regulatory limits. But I’m not entirely sure if my logic is correct, so I’d appreciate your thoughts on this.

Dr. Geis, I’d love to hear your comments on my situation. With your bachelor and doctoral degree in microbiology, expertise, and your previous experiences in the US Army and P&G, I am more than confident that I will learn so much from you. Thank you in advance for taking the time to read and respond to my message in this forum.

Please feel free to ask me more questions if you need more information. Additionally, please feel free to correct me if my logic is flawed.

I look forward to your response.

</div>