Penetration Enhancers- Which ones to use?

Unknown Member
edited March 2014 in Formulating
Hello everybody,

I would like to make a dermal tea tree oil formulation (<10%) in water, which also will contain a small concentration of surfactants to help solubolize the tea tree oil. In addition, I would like to add some agents to increase the dermal penetration of the tea tree oil.

My question is, what penetration enhancers do people recommend? I have read about propylene glycol,  diethylene glycol monoethyl ether, ethanol and oleic acid as all being good enhancers. So I may consider adding one or more of these at concentrations lower than 5%. 

Does anyone have experience in this topic?

Thank you for taking the time to read my post.


  • BobzchemistBobzchemist Member, PCF student
    Penetration enhancers can theoretically turn a cosmetic into a drug. 

    Personally, I would never recommend a penetration enhancer for use in cosmetic products, and particularly so for a home-crafter, unless you have the resources to professionally safety-test your formulations.

    Safe home-made cosmetics sit on the surface of the skin and do not penetrate. Ever. Anything more than that introduces an unacceptable health risk, in my opinion.
    Robert Zonis, Sr. Formulation Chemist, Beaumont Products "All opinions and comments expressed are my own, have no relation to Beaumont Products, are fully copyrighted, and may not be used without written permission."
  • Hi, what alpha bisabolol? That is advertised as a penetration enhancer safe for natural skin care? I was not aware oleic acid is a penetration enhancer... how can you use say almond, safflower or camellia oil if this us not safe? Or were you referring to synthetic enhancers?

  • Should ve *what about alpha bisabolol*
  • DavidWDavidW Member, PCF student
    I would say based on the info you provided your first problem is going to be getting you TT oil solubilized.  You don't say how much but you did say <10%.  Depending on how much less you are going to need a lot of surfactant or other items, not a small amount.
  • Thank you for everyone's responses.

    I have not come across alpha bisabolol but I will look into it. Oleic acid has been shown in a couple papers I read:

    Gao 1998 Effect of oleic acid/ethanol and oleic acid/propylene glycol on the in vitro percutaneous absorption of 5-fluorouracil and tamoxifen and the macroscopic barrier property of porcine epidermis

    Clarys 1998 In vitro percutaneous penetration through hairless rat skin: influence of temperature, vehicle and penetration enhancers

    Trommer 2006 Overcoming the Stratum Corneum: The modulation of Skin Penetration

    Has anyone used any penetration enhancers before? If so, could you describe your experience with one of them?

  • chemicalmattchemicalmatt Member, Professional Chemist

    Though philosophically I'm with Bob Zonis on the subject, here are some cues I've experienced.  Liposomes (phospholipid vesicles you can make with lecithin) are designed to penetrate the stratum corneum while carrying a "payload" of vitamin E or whatever lipid can fit within.  Emu oil (kalaya oil in some parts) has pronounced penetrating properties and has even been known to cross the blood-brain barrier.  Ethoxydiglycol has the property of enhancing penetration of the hair cuticle inot the cortex with small molecule components (e.g. NaOH, LiOH).  Unfortunately, it also halps penetrate the scalp with those same alkali - ouch!  Then there is that isosorbide ester ICI (now Croda) has that allows triglyceride oils to penetrate into the subcutaneous layer. I forgot its name.

    (Hey Perry, now that the glaciers have receded from North Avenue here in Chicago, start joggling again, clear your brain with fresh air, and come up with an article about this topic.)

  • DMI is good penetration enhancer..
  • chemicalmattchemicalmatt Member, Professional Chemist
    Yup.....that's the isosorbide thingy allright.  Arlasolve DMI (dimethyl isosorbide)?  Not an ester either, but a modified heterocycle. Another strangely expensive chemical too if I recall. Even more so now that Croda markets it, I suspect.
  • MicroformulationMicroformulation Member, Professional Chemist
    Grant also supplied Dimethyl isosorbide (Gransolve DMI). Microformulation Cosmetic Consulting provides Custom Formulations for both large Commercial accounts as well as smaller entrepreneurs. We can provide Naturally compliant Formulations under the NSF, NPA, Whole Foods and USDA Organic Certifications. BS.Pharm Albany College of Pharmacy, Union University.
  • BobzchemistBobzchemist Member, PCF student
    Ordinarily, I'd stay out of a discussion like this. However, a major concern here is that Tea Tree Oil is one of the few essential oils that is far from harmless.

    Tea tree oil can be toxic if ingested. Using a penetration enhancer to get it further into the skin, where it might be absorbed into the bloodstream, strikes me as being a Very Bad Idea. 
    Robert Zonis, Sr. Formulation Chemist, Beaumont Products "All opinions and comments expressed are my own, have no relation to Beaumont Products, are fully copyrighted, and may not be used without written permission."
  • I work with penetration enhancers a long time and never had any particular problem ie skin irritation, rushes. 

    Penetration enhancers could be divided into two groups. 

    1. Synthetic 
    2. Natural

    1.Synthetic: DMI (dimethil isosorbide), Ethoxydiglycol, Ethanolic Compounds, Azone, DMSO, MSM, Isopropyl Myristate are among the best there are with DMI being the most expensive one followed by Azone. Azone is the most recent one and looks very promising as it was specifically designed to do just that: facilitate the entrance of actives (both hydro and lipophilic) into the skin. DMSO (dimethyl sulfoxide) is very strong and effective but avoid it for face-creams, only for topical use like pain relieve emulsions. Ethoxydiglycol works both as a penetration enhancer and as a solubiliser being capable to solubilise both lipo and hydrophilic actives. 

    2. Naturals: here the list is very wide as there are many oils that have penetration enhancing capabilities along with essential oils and a few solids/dry extracts. Jojoba oil, Olive oil, Macadamia oil, Emu oil etc. Oils rich in Oleic and Palmitic Acid are good for both feeding the skin and carry along actives into the skin. Jojoba and Macadamia oils are the best for penetration enhancers. Also, essential oils are very good penetration enhancers as they are rich in terpenes. Most powerful ones are the essential oils of Black Cumin and Wintergreen. However they smell weird and as a result they cannot be used for face emulsions even at low concetrations (wintergreen gives a burning sensation as it contains high levels of camphor) . Other EO with good penetration enhancing capabilities include Tea Tree, Eucalyptus, Lemongrass, Peppermint, and the list is quite big. The problem with EOs is that they smell and as a result they can be used only at low concentations. I have created and tested emulsions for face applications containing TeaTree oil with concentration up to 1%. No side effects were ever reported. The emulsions were for acne, the TeaTree oil worked as an antiseptic, an antibiotic, a penetration enhancer. 
     A-bisabolol  natural-derived (there is synthetic too but less potent) is known for being both good antinfiammatory and penetration enhancer. Urea also is good for penetration enhancer and humectant but in concentrations over 5%.Among the dry extracts that can work as a penetration enhancer is the dry extract from Sabinsa-Tetrahydropiperine, it is the dry extract of Black Pepper I think, purified. It contains at its purest form the substance that gives pepper its burning sensation, however Tetrahydtopiperine does not give any burning sensation as it is used at very low concentrations 0.1% and it enhances the entrance of hydrophilic actives. Capsacaine or Capsicum (dry extract of Red Pepper or Chilly) also is good for penetration enhancer but only for body applications as it is well known for how it burns. Finally, a-lipoic acid can be used as a penetration enhancer but at concentrations over 2%. The main problem would be that it has a bad smell and it would give yellow colouring on the emulsion. 
  • MarkBroussardMarkBroussard Member, Professional Chemist
    edited August 2019
    I've used Emu Oil, Oleic Acid, MSM and Phospholipid-encapsulated "actives," individually, and in combination with one another, with good success.  The best combination I've found to be Emu Oil + MSM + Phospholipids or Oleic Acid + MSM + Phospholipids.

    DMI has a horrid smell that is very difficult to mask.

    Chemist/Microbiologist formulating in the Organic & Naturals arena under ECOCert/Natural Products Assn/Whole Foods/National Organic Program guidelines focused skincare & haircare products. 

    See website for details
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