[Gunther]

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

[Gunther]

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

[Gunther]

Wacker’s Belsil P 1101 looks interesting
It’s supplied dissolved in alcohol, but who knows if the polymer itself is soluble in cyclomethicone.
https://www.wacker.com/cms/en/campaigns/special_effects/haircare/styling.jsp
https://www.wacker.com/cms/media/publications/downloads/6022_EN.pdf
https://www.wacker.com/cms/media/publications/downloads/6502_EN.pdf

I’ve just contacted Wacker, waiting for the reply.

[Gunther]

1. What’s the pH of your soap (after it’s diluted in water)?

2. What fatty acids do you use?
If they are cheaper than oil, and if they’re the right fatty acids, you can cut some costs by replacing some oil with extra fatty acids.

3. What is your competiton doing?
Are you the lowest priced option?

4. What other plants are grown in your area?
May I ask where are you located?

[Gunther]

Usually CETAC reduces viscosity
But you can try mixing some bare K-stearate with CETAC to see if they form a thick slime = sign of uncompatibility.

[Gunther]

Not much room for cost cutting
you can try to skip the middleman and buy oil directly from palm growers or pressers.
And even so, the cost reduction will be relatively small.

You can try also making some premium, higher priced, hot process soaps
that don’t have such a high pH, so they’re gentle to skin and hair, i.e. with coconut oil,
maybe their profits can help offset some economy soaps costs.

[Gunther]

1. 5% sles won’t properly thicken with salt, you’d need at least 7-8%.

2. SLES in a leave-on product will likely cause irritation and an unpleasant feeling.
Please consider switching to milder surfactants, or dropping surfactants altogether.

3. Is that a leave-on sanitizer i.e. alcohol gel
or just a liquid wash meant to be rinsed off?

[Gunther]

What’s the most significant cost, raw materials of the manufacturing process?

Have you considered slowly transitioning to hot process or rebatch?

[Gunther]

Thank you guys
At the end I ended up doing a titration with a pipette and pipette pump and pH paper (I don’t like dipping pH meters in strongly acid or alkaline solutions).
It took 0.4% of 50% NaOH (equal to 0.2% solid NaOH) to reach a mildly alkaline pH.

@Belassi thanks for the Bromothymol blue idea. Titration was slow as some solid debris (maybe solid NaOH coming out of solution) formed on contact with the acid, taking a bit to redissolve.

@ozgirl
May I ask why 50% NaOH is preferable to flakes?

Neutralization Information:
Temperature and pH must be controlled during neutralization of BIO-SOFT S-101 to prevent darkening of the product and corrosion of stainless steel equipment. The reaction temperature should not be allowed to exceed 50°C and the pH should not go below 6.5.
https://www.stepan.com/uploadedFiles/Literature_and_Downloads/Product_Bulletins/Surfactants/BIO-SOFT®/BIOSOFTS101.pdf

I wonder if this only applies to steel tanks?

[Gunther]

For saponification, you may wish to switch to coconut oil and Potassium hydroxide
Potassium cocoate is a bit water soluble unlike Palm soap
https://link.springer.com/article/10.1007%2FBF02645899
This will allow you to dissolve some soap, without needing a highly alkaline pH, which can damage skin and hair.

Also, palm oil has a bad reputation, unlike coconut. Thus allowing for easier marketing.

[Gunther]

First, see if it actually works and does something noticeable.

Then you can try cold extraction, boiling it and filtering
and extraction with alcohol (cold extraction, since alcohol is flammable).

[Gunther]

Ginseng
Powder mixed in hot water seems to work better than caps.
Get your Blood Pressure checked tho.

For some reason tea actually makes me relaxed and even drowsy.

If it’s a health problem:
1 Start by getting your metabolic rate checked
Temperatures on waking up in the morning, heart rate, and their drop after eating give important clues.
2 Get comprehensive thyroid labs. At least TSH, total T4 and T3.

[Gunther]

Unless your hair is chemically treated
i.e. dyed, bleached or relaxed
brittle hair often comes from healh conditions and there’s little cosmetics can do about it.
Hypothyroidism often makes hair thin and brittle.

OTOH some people have perfectly fine scalp hair, yet little or brittle beards.

[Gunther]

@Hicham do you plan to saponify palm oil?

[Gunther]

Can you make acceptable no-tear shampoo with SLES + CAPB at pH 7 ?

Is it true that pH 7.5 is milder to eyes than pH 7 ?

[Gunther]

What are the CIs?

Please try without the plant extracts, or try adding some antioxidant like BHT to see if it works.
You may need to wait several months to get the answer, so try to make as many different test batches as you can.

[Gunther]

You can check your local business directory for chemical suppliers

you can also contact the large manufacturers i.e. Kao, Pilot Chemical, Stepan, Clariant and often they will sell you as little as one drum, as long as you pick it up yourself.
Some are hard to do business with, i.e. Croda.

[Gunther]

@Dtmenson try only with coconut oil and Potassium hydroxide to see if it works
also, oleic acid is available cheap (IDK if purified oleic fits in your natural definition)

Palm kernel and shea butter saponification will yield mostly insoluble soaps, unless the pH is too high.

Please read the following study, and keep us posted if you find the whole study text

The solubility of sodium and potassium soaps and the phase diagrams of aqueous potassium soaps

Summary

Solubility data are provided and collected for the pure sodium and potassium soaps. Hydrolysis obscures the temperatures of solution but is obviated by the presence of a small excess of alkali. Each sodium soap has a large range of temperature between fair and high solubility, whereas the potassium soaps go abruptly into solution, at almost the same temperature and concentration of each soap.

The only soaps that are even moderately soluble at room temperature are potassium laurate, myristate, and oleate, the potassium salt of acids from coconut oil, and the sodium oleate. The other sodium and potassium soaps of the saturated fatty acids require elevated temperatures for solution.

Phase diagrams for the five commonest potassium soaps are developed and recorded.

https://link.springer.com/article/10.1007%2FBF02645899

[Gunther]

@Perry  @Belassi  fatty alcohols are maybe one of those substances where theory predicts they won’t do much (since they aren’t cationic), but at least they do something.

@amitvedakar  virtually all conditioners contain fatty alcohols.

[Gunther]

You can surf the major chemicals suppliers websites
i.e. Pilot chemical, Stepan, Clariant, Kao
print out some recipes
then write down the composition of the ingredients and concentrations they contain.

Some recipes are very good, some are mediocre
some make you buy unneded ingredients they make
but it’s a starting point.

[Gunther]

You’ll need penetration enahncers
but be careful, they may further damage skin.

https://www.researchgate.net/publication/289235811_Influence_of_isopropyl_myristate_on_the_percutaneous_permeability_of_ketoprofen

[Gunther]

Great @chemicalmatt I didn’t even know that Cetrimonium was an emulsifier too.
I always thought it was just a detangler.

@Kioko would you mind posting what was your formula like?

[Gunther]

The purpose was to replace as much water for cyclomethicone as possible
in order to get hair to dry faster.

BTMS was also used as a detangler/conditioner.

[Gunther]

IMO 9-10% BTMS might lead to very thick, almost solid like formulations
but who knows, maybe the other ingredients reduce its viscosity.

IDK if they used PEG-40 as a co emulsifier, or just as an oil source.

[Gunther]

Thanks @chemicalmatt I always keep on looking for the Like button when reading your posts.

I will keep on looking for dimethicone 200.

Yes, I prefer volatile silicones as they evaporate quicker than water.

Do you know if cyclomethicone can be used to dissolve anything other than silicones? i.e. hair holding polymers or cationic conditioners?
All my experiments seem to fail.