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Home Cosmetic Science Talk Formulating Advanced Questions Critique request for an uncommon “cosmetic product”: transdermal hormonal lotion

  • Critique request for an uncommon “cosmetic product”: transdermal hormonal lotion

    Posted by brightside on March 22, 2023 at 4:17 pm


    Due to a lack of accessibility of creams intended for transdermal hormone delivery (Versa Base, and others), I wanted to make my own lotion. I have been messing around with my own lotion formula, and I think I finally ended up on something that’s OK. However, since I know little about lotion making, besides what I’ve learned in the past two months messing around with it, I wanted to ask you guys to critique it and hopefully help me formulate something that’s even better.

    Since the goal is to deliver hormones through the skins, my lotion has a few requirements. 1. It has to hold at least 10% hormone. 2. It has to be effective enough at transdermal penetration to be worth using. 3. It has to not have ingredients that are too toxic.

    I would argue that my formula is superior to VersaBase, because VB lacks dedicated penetration enhancers besides the emulsifiers. While I have at least three. Propylene glycol and Lauric acid have shown synergism in certain studies for penetration enhancement of certain hormone analogues (much higher LogP, though). And the Nonanol showed an interesting disruption of the cholesterol in the lipid matrix of the stratum corneum.

    This is the formula I ended up with so far:

    Emulsifiers: Glyceryl Stearate SE - 4%, Eumulgin SG (Sodium stearoyl glutamate) - 1%, Stearyl alcohol - 2%.

    Penetration enhancers and solvents: Propylene glycol - 7%, Lauric acid - 7%, and Nonanol - 2%.

    Lastly, I am using roughly 10-15% of MCT as a filler oil, 0.5% of Limonene and Eucalyptol each for smell, mild preservative effect, and mild penetration enhancement, and 1% Vitamin E. And obviously, the 10-11% hormone. Also, Geogard ECT for a preservative.

    This creates a weirdly watery lotion, despite a massive ~50% oil phase, which is a result of the nonanol and propylene glycol. I added a touch of Stearyl alcohol to help stabilize it, because the nonanol seems to be doing the opposite of that.

    Question 1: Is propylene glycol part of the water phase? Since it’s actively solubilizing hormone, does that mean it’s attached to the hormone and therefore part of the oil phase?

    Question 2: Is there a way to bump the concentration up to 20% but prevent the waxy skin feel due to the hormone? I managed to make a 20% lotion simply by bumping the Lauric acid and PG up to 10% each, and cutting out the MCT, but the lotion turns out to be rather dry and waxy.

    Question 3: Is there any thing else that I should add/remove? Anyone have any advice or comments?

    Thanks all!

    brightside replied 2 months ago 6 Members · 17 Replies
  • 17 Replies
  • ketchito

    March 23, 2023 at 6:54 am

    Propylene glycol will for sure reside in the water phase of your emulsion.

    Regarding your emulsifiers, Glyceryl stearate SE has potassium (or sodium) stearate as emulsifier (Glyceryl stearate is a structuring agent) and that requires high pH to work as such, but your preservative system has two organic acids that require low pH to be in their active form, so you have a conflict there. Your lauric acid will probably be neutralized if you choose to use a high pH to favor your emulsifier, and might not work the way you expect.

    Also, limonene is a known allergen, so be careful with it. Check again your oil phase, not all the ingredients you mentioned are part of the oil phase.

    • brightside

      March 24, 2023 at 1:55 am

      Makes sense, but what happens to the hormone that PG solubilizes? Does it drag it out into the water phase? Because I’ve been messing around quite a bit, and the combination of fatty acid and PG are pretty effective in solubilizing the hormones. I’ve been adding it to the oil phase, and it can instantly make the oil phase go clear, solubilizing the hormone.

      Ahhh! That makes a lot of sense, thanks for that pointer. I basically might be making salts (or just reducing them?) out of the salicylic acid and the sorbic acid, rendering them ineffective.

      So what should I do about the emulsifiers? I need the lauric acid to be untouched, since its needed for penetration enhancement. Does it matter that I have a bit of the stearic salts? Some of the ingredients do prevent emulsification for a while, I think the nonanol and PG, but I do eventually get a decent emulsion that has been stable for around 3 ish weeks so far. Ideally, I would need roughly 6 months, after which It’s OK if it separates.

      As a side question, I have been wondering if the creation of an emulsion is increasing the capacity of the lotion. A 10% hormone lotion’s oil phase will crash once it cools, and the hormone will cloud the solution, but once I form emulsions, there are no signs of crashing, grittiness or dryness. Is it possible that the hormone is incorporating into the micelle wall? Kind of like cholesterol in lipid membranes. Or, I guess it could be dragged out into the water phase with the PG? Sorry if this is too much questions, I’m awfully curious 🙂

      Thanks for pointing that out too. I will keep an eye out for any skin reactions, and if anything, remove the limonene.

      • ketchito

        March 24, 2023 at 7:10 am

        The capacity of PG to drag your hormone into the water phase will depend on your hormone’s partition coefficiente.

        In the case of your emulsifiers, I’d choose a system that doesn’t require neutralization. I’ve seen Glycery stearate (and) PEG-100 stearate being used im topical creams, but you need to check which type of emulsifiers (or emulsions) are better to deliver your type of active (there are several papers on the matter).

        About your nonanol, I’m kind of concern. The point is that on the papers you linked, the delivery system is different (none are emulsions). Chances are that your nonanol would rather go and form part of the interface of the emulsion, and not perform as penetration enhancer. Lauric acid could also behave the same way (like Stearic acid does when it’s used). Penetration enhancers that @chemicalmatt mentioned are the most used and in this case, might seem like a better choice, but you can still test your system and perhaps compare it to one with those others 🤓

        @PhilGeis raised very good points. Also, how would you evaluate penetration of your actives? If I remember well, usually sections of skin or skin models are taken, and the active is extracted with solvents.

        • brightside

          March 24, 2023 at 5:39 pm

          By saying, “lack of accessibility of creams intended for transdermal hormone delivery” I meant that, as a regular citizen, I can’t buy VersaBase. I’m sorry I didn’t make it more clear, I am a DIYer, not someone trying to sell a product. I hope that’s OK! @PhilGeis

          My way of determining the effectiveness of a particular lotion is just to test it on myself. I have been messing around with various bio-active compounds for years, and generally have a good sense of things affect me. The lag time, required dose for the effect, and the duration of action all inform me of the effectiveness. If there would be a lab that could test something like this, it would be amazing, but for now it’s just subjective experience. That’s alright, though, since I am planning on personal use, therefore what works best for me, is the best formula (for me).

          Damn, that’s fascinating but also disappointing. I will definitely be looking into other emulsifiers and the penetration enhancers that @chemicalmatt suggested. It would not be possible for me to realize this by myself, and your guys’ comments have been very helpful. Thanks!

          If you have anything to add, I’m all ears.

        • brightside

          March 24, 2023 at 7:56 pm

          After thinking about it, I think I have three options.

          1. Do what you and @chemicalmatt suggested. Get a more potent penetration enhancer, get a better emulsifier, and stick to that.

          2. Attempt a micro-emulsion, since those seem to be highly effective in penetration as well.

          3. Make a solution that isn’t an emulsion, and add some thickener to make it easier to use. Like you said, if nonanol is incorporating into the emulsification, then I need to not make an emulsion. Could I use carbomer for this?


    March 23, 2023 at 2:57 pm

    sounds interesting! what is your background and purpose for this project? i am assuming you are working in pharma industry?

    i worked a while ago developing topicals with hormones so your question sparks my interest again 🙂

    • brightside

      March 24, 2023 at 1:33 am

      Actually, no. I suppose I can call myself a biohacker? I’m primarily looking to do a sort of DIY TRT for a few months, but I am also interested in topical P4, P5, DHEA, and maybe 5a-DHP. I know I can get a simple script for TRT, but I really don’t like that idea. I’m not particularly scared of needles, but I think it’s an incredibly primitive method due to its invasiveness. Transdermal hormone delivery seems like a much more elegant solution in my opinion.

      A large benefit of transdermal hormones and in particular T, is the reduced suppression and half life. With transdermal T, for example, you can achieve high blood levels for around a day but then bounce back in the next one or two days. Compared to the standard Test E which takes at least 2 weeks to completely flush out, transdermal T is much more attractive.

      Obviously the other hormones are different when it comes to suppression, but for whatever reason, I am just really attracted to the idea of delivering hormones through the skin using a cream/lotion. For example, I was planning to also make a P5 or P4 cream for my mom once I figure out the best recipe.

      That’s interesting. Could you tell me a bit more?

  • chemicalmatt

    March 23, 2023 at 3:22 pm

    A couple of considerations here. Which hormone are you delivering? Progesterone? Progesterone acetate? Other? Prog acetate will be lipid-soluble, while Prog natural more water dispersible with a logP< 5. Also, pentylene glycol and ethoxydiglycol are superior penetration aids to the others. As for amping up concentration, remember your system will always have a capacity limitation, so even 10% may be more than enough, the rest “left on the table” so to speak and hormones are very expensive, right?

    • brightside

      March 24, 2023 at 2:47 am

      Well, I was planning on delivering all kinds of hormones, but they are all <5 logP. I mean, none are esterified, although I am really curious to experiment with that too. I read somewhere that if your penetration enhancement is strong enough and your drug is lipophilic enough, then your bottle neck is the aqueous layers of skin past the stratum corneum. In that case, using esterified hormones would be really interesting, since you could prolong the duration of action because of the esters, and also achieve high absorption (since your penetration is so good, assuming the enhancers don’t deplete).

      Ok. I do have some reasoning behind my decision of PG/LA/and Nonanol. Take a look and let me know if I should switch to ethoxydiglycol or pentylene glycol. I’m not excited about using ethoxylated products, but the pentylene glycol does look interesting. I like PG because it’s carried to the liver and metabolized to lactic acid, which is harmless.

      So there is a study showing impressive synergism between LA and PG. I’m not copying their ratios, and have additional ingredients would probably skew results. The largest difference is that they were testing esterified and fluoridated hormone analogues which are much larger and have high logP of 12.

      Lauric Acid + PG study:

      Regardless, I used 1:1 of PG:LA mainly because it seemed to most efficiently solubilize the hormone at that ratio.( perhaps more PG is more effective, but too much screws with emulsification in my setup)

      I know that both are decent enhancers on their own, so I’m hoping to achieve some synergism, but if not, it’s OK. I still need a fatty acid and some kind of alcohol for solubilization.

      There is also this study which looks at fatty acids and their permeation enhancement of estradiol. LA is by far not the best, but I don’t like the idea of using MUFAS or PUFAS. I did try some oleic acid, but it went rancid too fast because of my carelessness. Even if I would have been really careful, it still came from the supplier already a tad rancid. Unless I can get a high quality supplier, I will stay away.

      Fatty Acid Study:

      Some of the other fatty acids do look like better options, but I picked LA mainly because it was easily accessible, not too smelly, and not too long which might create excessive thickness.

      Lastly, I picked nonanol because of two studies. The first one compared the medium chain fatty alcohols on melatonin absorption, and they all proved very effective. Nonanol was a good blend between low skin irritation and permeation enhancement. Now, that study used melatonin, but the second study compared various penetration enhancers on the uptake of estradiol, and undecanol proved very effective. The first study suggested that the medium chain fatty alcohols interfere with the cholesterol-cholesterol, and cholesterol-ceramide connections in the lipid matrix. If true, that means that nonanol would have a similar penetration enhancement as the undecanol. Both are roughly the same length as cholesterol (C9 vs C11), and both were a similar effectiveness in the melatonin study ( Decanol-C10 being the best).

      Melatonin Study:
      Second study:

      This way, I have an alcohol, a fatty acid, and a fatty alcohol that can interfere with cholesterol. As far as I understand, alcohols and fatty acids mainly disrupt or extract other fatty acids or ceramides, while the cholesterol is more resistant.

      Here are two of the tables from the fatty acids study.
      Also, a graph of the Fatty Acid study, and the “Second Study”. The graph is exactly the same, I just remade it to make it less blurry and have better readability.

      What do you think?

    • brightside

      March 24, 2023 at 2:51 am

      Reply to the last sentence:

      I assume that I won’t be able to get 100% absorption regardless, right? Or are you saying that if I push the % higher, but don’t dramatically increase my solvents and penetration enhancers, then there would be too much hormone to be effectively pushed/pulled through?

      And yes, they are quite expensive 🙂

  • PhilGeis

    March 24, 2023 at 5:58 am

    How do you propose to address safety and, if in us, regulatory compliance?

  • PhilGeis

    March 25, 2023 at 2:28 pm

    Your risk - but please be careful.

    • brightside

      March 28, 2023 at 5:02 am

      Yes, I will be. Thank you!

  • Pharma

    March 26, 2023 at 2:01 am

    That’s not a ‘cosmetic product’ but a pharmaceutical. If pharmaceuticals aren’t your field of expertise, I highly advise against using highly active pharmaceuticals.
    BTW good quality hormones are usually used in micronised form (happy inhaling when working with these) due their inherently bad solubility (which comes from their steroid/cholesterol-like core structure).

    • brightside

      March 28, 2023 at 5:00 am

      Yeah, you’re right. I didn’t know what to call it, so I put it in quotes.

      Yes, everything I have is micronized, some better than others. It’s not an issue. And neither is solubility, since I’ve reached up to 21% of some hormones (DHEA, which is one of the more simple ones in terms of solubility).

      Not sure what is so scary about potent actives as long as you have a clear understanding of what they are and what they do, but thank you for the warning.

      • PhilGeis

        March 28, 2023 at 5:44 am

        Not to be argumentative - but do you have that in depth understanding? Can you say what hormone do you have in mind and to what purpose. I’m certainly not much help in risk but think pharma can provide perspective..

        • brightside

          March 28, 2023 at 6:09 pm

          That’s not argumentative, but a fair question 🙂

          I won’t claim to know everything, especially since I don’t have formal education in this field, but I do know a decent amount about health in general, and have been learning about it for years at this point. I would say that I know more than the average guy on steroids, for sure.

          I’ve used things like pregnenolone and progesterone for years as well, and yes, I’m a guy. Occasional progesterone is very useful as a tool to relieve stress or excess catabolism. ( Dr. Ray Peat has some tremendous insight on this topic) Men make plenty of progesterone themselves and it’s not an exclusively female hormone. Many studies utilize progestins, so their conclusions are not always clear, since these progestins can often have estrogenic activity. Meaning, progesterone =/= progestins, and the studies need to be looked at carefully.

          I also don’t see any harm behind androgen use as long as it is within physiological ranges. A few mg of DHT can very nicely inhibit cortisol and estrogen, and in fact boost pituitary output to the gonads. While TRT level doses of T are mostly fine, and that has been shown to be useful in plenty studies already. The main concern with androgens, as far as I can tell, is prostate enlargement and excess aromatization. Both of these can be watched and managed.

          On the one hand, the argument could be made that I don’t know the real effects of long term hormonal manipulation. However, on the other, neither does anyone else who is exposed to the slew of environmental toxins which have hormonal actions as well. Take BPA, for example. It’s damn near unavoidable, and although it isn’t much of an issue acutely, it does provide a low grade estrogenic load over a long term. There are plenty of other “new” toxins which we are exposed to that we weren’t before. Many of them may be mild, but if you apply even a mild additional estrogenic load (that is, one that is exogenous) to a population, that means lower T levels for many men. This can become a problem for men who are in the lower end of the distribution. The results of lowered T are well known, and diseases such as T2D are more common.

          This is obviously a complex topic, and my paragraph doesn’t touch even 1% of it, but I hope you get my point. Hormonal intervention may be dangerous, but so is not having optimized hormones. ( and other health aspects, such as diet, vitamin/minerals status, sleep, and microbiome). Plus, opportunity cost is real and is something everyone pays anytime their health isn’t optimized.