Is there anything I can do to make this product actually effective on my skin?

MJLMJL
edited August 1 in Formulating
I’ve finally come to understand/accept that a formula I have recently been testing is basically just sitting on the very top surface of my skin.

My issue is I need to make a water based product for my skincare needs. I have really damaged skin which FREAKS out when I apply almost anything: oils, butters, fatty alcohols (cetyl, cetearyl), propylene & butylene glycol, thickeners & gums (carbomer, xantham gum), and more. 

I wanted to make a water-based serum with hyaluronic acid, niacinamide (research shows it can increase ceramide synthesis) and n-acetyl glucosamine (apparently a precursor to hyaluronic acid in skin, purported to increase moisture). And a preservative, of course.

My question is: Is it a waste of time to create a formula with these ingredients if they are just going to be sitting on surface of my skin? Will they produce any kind of effect at all on the quality of my skin?

On the other hand, I have also read that it is a myth that cosmetics travel and/or act much further below the stratum corneum. Are skincare products in fact supposed to act solely on the surface of the skin?

So I guess right now I’m just really confused as to whether or not I actually need it to somehow “penetrate” to a certain place in my skin for changes to take effect. 

If anyone can help clarify this for me, and/or if there are any ingredient suggestions that might make this product effective - I would very much appreciate the input. 

Thank you for your time.
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Comments

  • I agree with you that it is a myth that molecules migrate deep in the skin. Anyway that did not stop the pharmaceutical industries from developing methods and techniques to make it possible to send molecules via the skin. The easiest approach is to use penetration enhancers AKA adjuvants, they are molecules that help the transport of other molecules through the skin and/or help stabilize them enough. Another way is to encapsulate them (liposomes, silica spheres, ...). Just keep in mind that the adjuvants are specific to the molecule you want, so you may need at least one adjuvant per active ingredient.

    One example comes to mind: Lidocaine (in anesthetic creams) have a better effect and migrates easily through the skin in the presence of menthol. Another is honey and ascorbic acid, together they help regenerate collagen in the skin.
  • Thank you @ChemicalPyros and @Gunther for your comments and the information!
  • Hi MJL,

    The Ordinary adds Dimethyl Isosorbide to their Niacinamide serum to increase the penetration. Check their products. Since they are very effective I believe it can be used as a reference. Btw Glucosamine made my niacinamide serum orange. I posted a question here and still waiting for an answer.

    Also, both lotioncrafter and makingcosmetics have ceramides complex that you can add to your serum. It is my personal experience (I am not a chemist) but topical ceramides make difference.

    Best,
  • Penetration through the stratum corneum is not an easy task. 

    - Most enhancer of penetration (e.g. solvent, surfactants, alcohols etc) will damage the lipid matrix of the SC leading to a loss of hydration of skin, irritation and further skin and can cause long-term skin disorders.

    - Vesicles that are described to penetrate the SC are made with some surfactants and can lead to the same problems as described before.

    - Other lipid vesicles such as liposomes will not penetrate the SC due to their size. 

    - Use of mixture cholesterol/ceramide/fatty acids could be a good approach as it mimics the composition of the lipid matrix of the SC, but you have to be sure that these ingredients penetrate the SC


    An elegant method to penetrate the SC is proposed by Bicosome, they develop a unique technology made of lipids with composition similar to the lipid matrix of SC and that are structured in such a way that very small disks are able by their size/composition to penetrate the SC. 

  • "My question is: Is it a waste of time to create a formula with these ingredients if they are just going to be sitting on surface of my skin? Will they produce any kind of effect at all on the quality of my skin?"

    Based on the evidence available, I do think it is a waste of time. These are claims ingredients that will just sit on the top of your skin and do little more than moisturize. 

    You'll have difficulty showing any improvement better than just using a moisturizer alone.

    Although, I'd be happy to be shown wrong based on scientific evidence. I just haven't found any convincing evidence that under real-life conditions, things like Ceramides, Hyaluronic Acid, most vitamins, stem cells, or most any other anti-aging ingredient, actually has much noticeable effect.

    The only ingredients that seem to have some merit are retinols (the drug kind) and niacinamide. I still find the later dubious but there is at least more than a little evidence of effectiveness.
  • @MJL Based on what you write with skin that is so damaged that it "Freaks Out" (which I read as; invokes an inflammation) on contact with nearly anything, you should consider visiting a dermatologist who will likely prescribe something along the lines of a corticosteroid to reduce inflammation.

    As for the question "is it a waste of time", from what I've read, a lot of formulations actually allowing for water-soluble "actives" to show penetration beyond the stratum corneum are formulated with a high level of emollients and oils to "force" what lies beneath the oily layer to migrate into the skin where it is more favorably dissolved than in the oil-phase.

    @Perry There are available peer-reviewed scientific studies on the efficacy of ingredients (even positive ones), but I think the most difficult part about scientific evidence of cosmetic efficacy, is that sponsors and authors are usually working for a specific company and experimenter bias is a real hindrance, and I my opinion only double-blinded studies can be trusted.


    Dabbling Formulator — Qualified Cosmetic Safety Assessor — experienced in claim substantiation & EU regulatory affairs.
  • I just new in cosmetics
    but selecting the ingredients which have molecular small comparing the pores. 
    Go with natural. Minimize adding additional ingredients that are not benefit for skin.
  • For example, for reduce pH, we usual add TEA or Na0H. Do not do that.
    dilute the AHA or BHA to near desired pH
  • @Sibech - Yes, I'm aware of many studies. I just find them lacking. Most are done on cell cultures or without controls or on small groups. I agree double-blind are the most reliable.  But even for those I'd like to see replication of studies which you rarely ever get.

    Like you said, most of the research is done by companies or sponsored by a company. This doesn't mean the research is crap but it does mean we have to be extra skeptical. Plus, there is the file-drawer effect where researchers don't publish negative findings.

  • I wish there were more proponents of "admitting failures" in all scientific fields. I get the financially-driven reasons to keep negative findings quiet, but ultimately reporting conditions that didn't produce intended results could save time and money. And as @Perry mentions, one study doesn't make anything conclusive, positive results or not. One of our core beliefs as scientists is in reproducibility and that should apply in all cases. Always disappoints me when personal gain wins out over progress and learning for science as a whole, but c'est la vie or whatever.
  • @EVChem I think the problem is not only person gains and financial reasons, I think a lot of journals would be hesitant about publishing negative findings - It doesn't bring a lot of exposure to the journal. My guess would be a higher proportion of such papers in open access journals.

    @Perry Can't you and Randy make "The International Journal of Negative Findings" with Brains publishing? - Think of all the subscription fees from Libraries.
    Dabbling Formulator — Qualified Cosmetic Safety Assessor — experienced in claim substantiation & EU regulatory affairs.
  • I will weigh-in on this all, much as I have in the past. One of my first University Internships was with Ciba Geigy doing QC sampling and QC Testing of Trans Derm Nitro patches. IT IS NOT EASY TO GET PRODUCTS TO PENETRATE INTO THE BODY. We did it based on established and complicated Calculus-based Pharmacokinetic Formulas. It relied upon a strong concentration gradient (much more active material in the reservoir of the patch), an engineered membrane with known channel properties, actives with very small molecular sizes (<500 daltons) and other proprietary processes and materials. It is naive and contradictory to Pharmacokinetic principles to believe that you can effect any real penetration or that you can establish a significant blood/plasma concentration with a simple topical product.
    markfuller@microformulation.com Microformulation.com 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.
  • This!!!! ^
    Couldn't agree more with @Microformulation
  • @Microformulation well that's depressing but honestly something I think most of us know in the back of our heads. But I don't think that skincare is all snake oil and magic marketing claims. There are ingredients that have shown promise (niacinamide comes to mind) through simple topical application. Then again,there is the poorly-hidden elephant in the room of cosmetics: our products are  not supposed to penetrate/to modify the skins function.They are only meant to hydrate.But that's a whole new discusion so I'll leave it at that.
  • A very insightful and interesting discussion, loved it. 
  • Interesting study
    glyceryl monocaprylate/caprate beats IPM as a penetration enhancer

    Glyceryl monocaprylate/caprate as a moderate skin penetration enhancer
    Paul ACornwellJoeTubekHans A.H.Pvan GompelChris JLittleJohann WWiechers

    https://doi.org/10.1016/S0378-5173(98)00194-XGet rights and content
    Abstract
    Eleven widely used lipophilic formulation excipients have been screened for their skin penetration enhancing effects. The excipients tested were glyceryl tricaprylate/caprate, isopropyl myristate, glyceryl monocaprylate/caprate, decyl oleate, polyethylene glycol-6 glyceryl dicaprylate/caprate, isopropyl isostearate, isostearyl isostearate, glyceryl monoisostearate, polyglyceryl-3 diisostearate, vegetable squalane and isostearyl alcohol. Excipient effects were evaluated by measuring skin permeability coefficients towards a model hydrophilic drug, 5-fluorouracil (5-FU), before and after a 6-h treatment with neat excipient. The skin penetration enhancing mixture, 10% (w/w) Azone® in propylene glycol, was used as a positive control. Only one excipient, glyceryl monocaprylate/caprate, had enhancement effects significantly above the buffer control (p<0.05). This excipient increased 5-FU penetration 10-fold. log Poctanol/water and hydrophilic–lipophilic balance values were calculated for each of the excipients. It was concluded that, of the excipients screened, glyceryl monocaprylate/caprate is the only penetration enhancer because (1) it is the least lipophilic, (2) it has surfactant properties, and (3) it has the optimum alkyl chain length for surfactant-type skin penetration enhancers. Since glyceryl monocaprylate/caprate has only moderate enhancement effects, it should be useful as a mild, well-tolerated skin penetration enhancer.

    https://www.sciencedirect.com/science/article/pii/S037851739800194X
  • Cutaneous Penetration–Enhancing Effect of Menthol: Calcium Involvement
    AmitJoshiAbhayJoshiHirenPatelDoveniaPonnothGraziaStagni

    Abstract
    Menthol is a naturally occurring terpene used as a penetration enhancer in topical and transdermal formulations. Literature shows a growing interest in menthol’s interactions with the transient receptor potential melastatin 8. A decrease in extracellular Ca2+ due to the activation of the transient receptor potential melastatin 8 receptor produces inhibition of E-cadherin expression that is responsible for cell-cell adhesion. Because calcium is present in the entire epidermis, the purpose of this study is to evaluate whether the aforementioned properties of menthol are also related to its penetration-enhancing effects. We formulated 16 gels: (i) drug-alone (diphenhydramine or lidocaine), (ii) drug with menthol, (iii) drug, menthol, and calcium channel blocker (CCB; verapamil or diltiazem), and (iv) drug and CCB. In vitro studies showed no effect of the CCB on the release of the drugs either with or without menthol. In vivo experiments were performed for each drug/menthol/CCB combination gel by applying 4 formulations on a shaved rabbit’s dorsum on the same day. Dermis concentration profiles were assessed with microdialysis. The gels containing menthol showed higher penetration of drugs than those without whereas the addition of the CCB consistently inhibited the penetration-enhancing effects of menthol. In summary, these findings strongly support the involvement of calcium in the penetration-enhancing effect of menthol.

    https://www.sciencedirect.com/science/article/pii/S0022354917302290
  • The effect of urea and taurine as hydrophilic penetration enhancers on stratum corneum lipid models
    Muellera1J.S.L.Oliveirab1R.Barkerc2M.TrappdA.SchroeteraG.BrezesinskibR.H.H.Neuberta

    Highlights
    Effects of urea and taurine on SC lipid structure are studied deploying a wide panoply of techniques in 2D/3D model systems.

    Urea and taurine do not fluidize the very rigid SC lipid structure.

    Under special conditions, urea and taurine are able to form pore-like structures in the SC lipid membrane.

    The penetration enhancement effect of urea and taurine in the SC must be related with the corneocytes.


    Abstract
    To optimize transdermal application of drugs, the barrier function of the skin, especially the stratum corneum (SC), needs to be reduced reversibly. For this purpose, penetration enhancers like urea or taurine are applied. Until now, it is unclear if this penetration enhancement is caused by an interaction with the SC lipid matrix or related to effects within the corneocytes. Therefore, the effects of both hydrophilic enhancers on SC models with different dimensionality, ranging from monolayers to multilayers, have been investigated in this study. Many sophisticated methods were applied to ascertain the mode of action of both substances on a molecular scale. The experiments reveal that there is no specific interaction when 10% urea or 5% taurine solutions are added to the SC model systems. No additional water uptake in the head group region and no decrease of the lipid chain packing density have been observed. Consequently, we suppose that the penetration enhancing effect of both substances might be based on the introduction of large amounts of water into the corneocytes, caused by the enormous water binding capacity of urea and a resulting osmotic pressure in case of taurine.

    https://www.sciencedirect.com/science/article/pii/S0005273616301845
  • @Gunther - how is the penetration effect measured?

  • @Microformulation first and foremost - you are absolutely right. But you do mention one thing "it is naive to believe that you can achieve a significant plasma concentration (percutaneous absorption)".

    However, that does not (necessarily) exclude dermal absorption into the epidermis where some marketing additives could arguably have an effect on stratum basale for instance (assuming they are druglike in structure).
    And some compounds if formulated well can also gain systemic access (although unlikely to be significant).
    Dabbling Formulator — Qualified Cosmetic Safety Assessor — experienced in claim substantiation & EU regulatory affairs.
  • @Sibech The absorption of products across the skin are complicated processes for which we use specialized calculus-based Pharmacokinetic mathematics models to understand and quantify the factors.  When discussing the modeling, we consider the scenario as a "two vessel" simplified system.

    Imagine a vessel with some limited permeability characteristics (the skin in this simplified model) suspended into another tank (vessel, here the actual blood/plasma). The first vessel contains a high level of the active and the main vessel (the blood/plasma) contains zero active ingredients.

    Through the broad actions of homeostasis, the two vessels will "want" to reach a state where the concentration is the same in both vessels.

    Now we must consider the factors. The concentration gradient (the relative difference in the active between the secondary suspended vessel and the blood/plasma vessel), the size of the active, the properties of the semi-permeable membrane and other factors apply. Since we are dealing with a delta (change) equation, the math is Calculus-based. Even in my Junior Year when Calculus was fresh and I had just aced Pharmacokinetics/Biopharmaceutics in College, the math was involved and in fact, for a whole summer internship, I sat in a windowless room doing this math on the Ciba Geigy QC line. It is not for the light-hearted.

    My overall point is that facilitating and designing the transport of an Active be it Pharmaceutical or Cosmetic is not an easy process and easily out of the skill set of most if not all the participants in this blog. In fact, I would probably need to review Calculus myself and I have actually done it in the past. It is also a bit puzzling since many of the people seeking to do it in an unqualified manner usually start in Cosmetics asserting "60%/70%/95% (heard them all) of what you put on your skin gets absorbed into the body." Then they pivot and say, "Let me add this penetration enhancer and get this complicated botanical consisting of hundreds of compounds into the body" since it is natural. THIS IS A PROCESS THAT SHOULD NOT BE ATTEMPTED WITHOUT HIGH-LEVEL UNIVERSITY TRAINING AS WELL AS INDUSTRIAL SUPPORT.

    "However, that does not (necessarily) exclude dermal absorption into the epidermis where some marketing additives could arguably have an effect on stratum basale for instance (assuming they are druglike in structure).
    And some compounds if formulated well can also gain systemic access (although unlikely to be significant)."
    Yes, but you shouldn't. We are making Cosmetics and it is a much more involved process than any allow. Likely, I could do the research and make a small crude nuclear reactor next door to you. The documents are declassified and I could use a Medical isotope in some crude manner.: SHOULD I TRY?




    markfuller@microformulation.com Microformulation.com 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.
  • @Microformulation I appreciate your simplified pharmacology lesson for other readers, I wish I had thought of adding that.

    I agree that we are making cosmetics. Unfortunately, there is a certain level of dissonance caused in part by differing regulations (To overly simplify, I do not consider sunscreen a drug). 

    While cosmetic products with some level of efficacy usually enter into a borderline territory, the compounds added to the skin may, in fact, have an insignificant level of effect on physiological or metabolic function.
    (Even adding pure glycerin to the skin would as it changes the osmotic pressure causing increased TEWL).

    "My overall point is that facilitating and designing the transport of an Active be it Pharmaceutical or Cosmetic is not an easy process and easily out of the skill set of most if not all the participants in this blog."
    You might very well be right, I have participated actively for long enough to make a proper judgement on that.

    " 'Let me add this penetration enhancer and get this complicated botanical consisting of hundreds of compounds into the body' since it is natural. THIS IS A PROCESS THAT SHOULD NOT BE ATTEMPTED WITHOUT HIGH-LEVEL UNIVERSITY TRAINING AS WELL AS INDUSTRIAL SUPPORT."

    Once again I agree with your notion.
    Should the "90% is absorbed" and "Natural is safe" people who pivot and say "Let me add this penetration enhancer for a botanical" decide to attempt such a move, they would likely be disappointed anyway.
    That is unless they have the required training to understand and elucidate the composition of their botanical, then manage to find structural analogues for which penetration enhancers are discovered. Otherwise, they would need a deep understanding of thermodynamics or be shooting in the dark when it comes to finding a penetration enhancer as those tend to be fairly specific.

    "Likely, I could do the research and make a small crude nuclear reactor next door to you. The documents are declassified and I could use a Medical isotope in some crude manner.: SHOULD I TRY?"
    More crude than the nuclear reactor would be is this thinly analogy-veiled threat.

    What you are arguing, as I see it, is essentially This is difficult and not safe for people without proper experience and technical support, therefore it shouldn't be done and that I agree with - but I fundamentally disagree with your original statement of "It is naive and contradictory to Pharmacokinetic principles to believe that you can affect any real penetration or that you can establish a significant blood/plasma concentration with a simple topical product." because it is factually wrong.

    To reiterate:
    I am NOT saying that it is easy.
    I am NOT claiming it is safe.
    I did NOT suggest that systemic absorption was likely.

    It is fine to state how difficult it is to design - because it truly is. But saying that it is contradictory to pharmacokinetic principles to effect any real dermal penetration is — while an uphill fight — factually incorrect. 
    Dabbling Formulator — Qualified Cosmetic Safety Assessor — experienced in claim substantiation & EU regulatory affairs.
  • Hello everyone! I ended up not logging on for the majority of August (thinking this post wouldn’t get much more activity than the first few comments) and was very surprised to come back to a full discussion on this post!

    I just wanted to say thank you so much to everyone who posted here with such helpful and insightful information and discussion. It means so much to me that you all took the time to come here - whether to respond directly to me, or to contribute to the discussion amongst members here. So thank you very much again, I so much appreciate the opportunity to learn from all of the information gathered here! 
     
    @Chemist77
    @Gunther
    @Microformulation
    @EVchem
    @Sibech
    @Perry
    @jeremien
    @ngarayeva001
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