Home Cosmetic Science Talk Formulating Can these penetration enhancers be used at a low pH?

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  • Can these penetration enhancers be used at a low pH?

    Posted by ETcellphone on March 29, 2021 at 1:58 am

    I am piggybacking somewhat off of my last post on penetration enhancers. For my vitamin C+E+Ferulic serum, which is a pH of 2.5-3, would any or all of the following penetration enhancers work in this low of a pH formula? : 

    tetrahydropiperine (THP)
    Dimethyl Isosorbide (DMI) 

    Pharma replied 3 years, 2 months ago 8 Members · 10 Replies
  • 10 Replies
  • Pharma

    March 29, 2021 at 5:04 pm
    Depends. Unless someone actually measured penetration of your three ingredients using said three penetration enhancers, there is no way telling whether or not they work. The issue with penetration enhancers (especially solvents like DMI and ethoxydiglycol) is that they may actually increase too much or even decrease penetration. If you look at scientific literature, using penetration enhancers can lead to seemingly great disappearance of the ‘active’ from skin surface but just bind it in the top layer or transport it into the blood stream. In either case, the intended action of your three constituents will be toast.
    Apart from that:
    - Low pH will already help with skin penetration of acidic actives (ascorbic and ferulic acid) whilst penetration of tocopherol won’t change between acidic and neutral conditions. Given that your solvents aren’t pH active, there will be no difference in penetration from a simple logic point of view.
    - Tetrahydropiperine might just be another hype. There is one publication (from the patent holders) and their data on skin don’t convince me. Found it also on the Cayman Chemicals HP with a reference to skin penetration. Piperine is a gastrointestinal absorption enhancer for some compounds with still unknown modes of action. However, the postulated ones of piperine, unlike mentioned in said publication, have nothing to do with skin absorption. The only exception I know of is that for heat sensation (THP is about 6 times hotter than piperine) which causes increased blood flow. Whether or not chemical modification would prevent or even increase penetration enhancement remains to be demonstrated properly. Meaning, there is no neat answer to your question without proper measurements.
  • chemicalmatt

    April 1, 2021 at 4:40 pm

    Ethoxydiglycol: no problem. DMI is also stable at that pH but is best employed as a lipid carrier. Cost ratio of of DMI:ethoxydiglycol is ~ 15:1 so choose your penetrant.


    April 1, 2021 at 5:07 pm

    ethoxy diglycol has skin irritation issues so use level restricted as per application via CRB-dmi has odor in creams/lotions which can be masked but suggest going Green with pentylene glycol ie Hydrolite 5 Green-Symrise

  • natiyo123

    April 24, 2021 at 9:19 am

    isopropyl myristate and triacetin are penetration enhancers and can work in acid pH

  • ngarayeva001

    April 25, 2021 at 6:10 pm

    Sorry if it’s considered off-topic, but does anyone know why ethoxydiglycol is restricted to rather small amounts in EU? I only found some papers mentioning kidney toxicity but no details. I am using it at 30% in CE ferulic serum (got inspiration from L’Oreal’s patent for personal use), and it’s ehoxydiglycol that makes it feel ‘right’.

  • Pharma

    April 26, 2021 at 7:24 am

    The issue with ethoxydiglycol is that it may contain considerable amounts of ethylene glycol as impurity. Ethylene glycol is metabolised to oxalic acid and that’s usually the compound which harms.

  • MarkBroussard

    April 26, 2021 at 12:34 pm


    First off … you should raise the pH of your concoction to 3.3 - 3.5.  Ethoxydiglycol or Pentylene Glycol + N-Acetyl Tyrosine would work well as penetration enhancers for this type of formula.

    I would encourage you to study the CE Ferulic patent for additional insight.

  • Dreamer77

    April 28, 2021 at 7:25 am

    I would use DMI at 5% paired to EDG at 2%. THP would not make any difference as it is destined for hydrosoluble ingredients only. Also, I would raise pH to 5.0

  • Dreamer77

    April 28, 2021 at 7:27 am

    You can also try Menthol Nicotinate at 0.5% to avoid redness on skin

  • Pharma

    April 28, 2021 at 8:05 pm
    First, you have three very different ingredients with very different characteristics influencing skin penetration. There is no one size fits it all (unless you use carrier vehicles or chemical derivatives).
    Don’t raise pH above 3.5 as this is said to be the upper end of dermal penetration of ascorbic acid. However, you might want to use a derivative which has a better topical bioavailability rather than blindly choosing a molecule which may or may not increase penetration of certain compounds.
    Ferulic acid doesn’t need a penetration enhancer, at slightly acidic pH it readily penetrates skin.
    Tocopherol on the other hand is highly lipophilic and you may have to resort to anhydrous formulations or nanocarriers like liposomes. As a fun fact: Tocopherol is a penetration enhancer for certain pharmaceutical compounds.
    Read through publications rather than simply picking a magic ingredient X recommended by someone who most likely never measured how much of your three ingredients respond how to the proposed additives. However, if it’s all for claims and giggles… take whatever you feel most comfortable with.

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