[Pharma]

Here’s the rest:

THE most important thing is to restore skin barrier
function! As long as your dog has skin lesions, all kind of dirt,
chemicals, allergens, bacteria, and so on will enter/penetrate his skin
and hence worsen symptoms. That’s why fairly often, strong cortisones
are applied for a few days and then paused; such an interval treatment
reduces long-term side effects (e.g. reduces skin barrier function) and
still suffices to break the vicious cycle of allergy  (dog) or
inflammation (human) -> reduced skin barrier -> entering of
allergens -> boosted allergy/inflammation -> more/stronger lesions
-> and so on.

From my perspective, your product is all
about hydration and not enough occlusion to keep moisture in the skin
and the bad stuff out of it. That product is okay to keep a dog from
getting all greasy but probably/likely not enough to protect his skin.
It might soothe the itching but the effect will neither last nor prevent
(especially because you can’t/shouldn’t wash your dog on a daily
basis). Therefore, I would add ingredients which restore skin barrier
and not just restore moisture. But, as said before, these may be better
applied separately as cream/lotion/serum. Furthermore, you’ve got way
more effect for your money from a concentrated leave-on than a diluted
rinse-off product.

[Pharma]

@Belassi: Do I understand it right that you’re using some kind of 1:1 shower gel-yoghurt mixture as… shampoo? ointment? cataplasm?

I do have dogs too. Actually, if you put the 4 lil guys on top of each other, they make up half a real dog :smiley: . Anyway, I’m familiar with skin problems because we have a candidate as well and a friend with an atopic cat. I don’t know if you already did everything, but I’m going to unroll your case anyway (I’m a pharmacist, I can’t help it):

1. Did you or the vet diagnose AD?

2. Has a zinc deficiency been excluded? Blood sample or trial-and-error zinc supplementation?

3. Have food allergies been excluded? Skin/blood tests, strict exclusion diet?

Regarding point 2. and 3.: Many if not most inflammatory/pruritic skin diseases in dogs but also cats are caused by either (food) allergies (very often it’s cow meat of all things, forage mites, flea, and with cats also perfumes -> ask, if you want to know more or read for example THIS article) and/or zinc deficiency. Zinc-responsive dermatosis is a fairly widespread but often neglected phenomenon and often manifests by causing and/or boosting skin conditions similar to AD, read for example HERE.

4. Antimicrobial treatments should be done only upon advice of a vet.

Calendula and TTO are mildly disinfecting and anti-inflammatory and a good thing to try (unless your dog is allergic against one of these). TTO may however worsen AD symptoms (you never know with AD anyway). If it doesn’t, you may try up to 5% if it’s not used on a large skin area but only for smaller acute patches. Mind, only increase it gradually and try a higher concentration always on a small patch first and don’t use it at high concentration day-in-day-out as prevention but for treatment of acute episodes only! 0.5-1% TTO should be fine on a daily basis and on large areas but there’s no toxicological data available except IIRC for some oral intoxications.

5. Yoghurt as is may be beneficial for certain types of AD. Though it’s not just the lactic acid inside. If you’re only after lactic acid: I would leave it out of the formula and treat my dog separately with A: a mild shampoo without all the fancy stuff except TTO, and probably glycerol and urea (because they’re cheap and hydrating and if they don’t work, they don’t harm either), B: apply the actives as serum/lotion/cream separately, and C: try yoghurt alone on acute patches. Try and see, that’s all you can do with AD.

Mild anti-inflammatory drugs like NSAIDs as mentioned by @Gunther would be a good trial for human skin inflammatory diseases. But since canine AD is an allergic disease which only resembles human inflammatory skin diseases and shares its name, anti-inflammatory drugs won’t do that much unless we’re talking strong stuff like cortisone and immunosuppressants which are a last resort choice. On the other hand, anti-allergic drugs such as antihistamines (topical and/or oral) are far better to start with: Talk to your vet! Since I’m not familiar with your case, I don’t dare recommending possibly harmful chemicals for your dog. Since human and canine AD aren’t comparable and the underlying mechanisms poorly understood, extrapolating from humans to dogs is neither the smartest idea nor very fruitful. For example that vitamin D treatment has no viable basis in dogs.

AD stands for ATOPIC dermatitis. Atopic is a camouflage-term which makes the doctors look smart although it basically says that we don’t know sh** about it. Psoriasis, as much as it sucks, has one good thing AD hasn’t: it’s pretty much the same in every patient. AD on the other hand is extremely individual, what helps one patient may worsen the symptoms in another. It’s always trial and error except for the “restore skin barrier” part, which is the most important thing to do, in human and in canine AD. The HOW on the other hand is, again, different for everyone. Use mild occlusion with as few potentially harmful additives as possible; for some, paraffin and vaseline are great, for others the skin needs to breath and light creams with natural oils work better. For humans and dogs, polyunsaturated fatty acids have proven helpful because they modify inflammatory (in humans) and allergic (in dogs) reactions. Hence, try some “healthy” oils on your dogs food and fur! Ours does very well with black caraway oil (Nigella sativa) as a food supplement. We have to use antihistamines and cortisone as good as never since he get such oils every day (and I was laughing at first about the “Try black caraway, it’s trendy and someone on Facebook said it helps”). Linseed, evening primrose and sacha inchi (Plukenetia volubilis) oil and the like work too but are less often used against allergies allegedly due to lacking traditional use (although, allergies have no traditional use). Anyway, there’s fair scientific background and vast practical experience by the public and their pets.

Because of an alleged cortisone-like mode of action, Cardiospermum halicacabu is en vogue right now (HERE’s an example which also uses sacha inchi oil). Probably, marketing simply makes people using these usually mild and “label-friendly” creams on a daily basis although they are poorly made from a cosmetic point of view (tacky, occlusive, perfume-free/stinky, no fancy skin feel etc.) and it’s simply the good compliance what makes it work and not cardiospermum extracts or even homoeopathic cardiospermum potencies.

I’m unsure what to think of licorice… I don’t know if glycyrrhizin really has pharmacological actions if applied topically (theory say it doesn’t). Today, I received a parcel with a vial of licorice extract, what a coincidence. I’m going to try it in a cream for my wife (who doesn’t have AD) and never thought of using it on my dogs. I received other stuff too that I’m probably going to try on them (I’m very curious about gamma oryzanol and Plandool MAS).

Pegylated silicone and oil derivatives: I don’t know (I’m honestly biased regarding these cause I’m one of those label-friendly first guys)… you have to try if your dog does better with this or that kind of oil or modified oil. Might work as well as it might not work. For some skin conditions, mineral oil based products are still the first choice. Silicone oils feel great and have unique properties unlike anything else but IMHO are about perception and skin feel rather than therapeutic usefulness. PEG’s offer other benefits such as respiration and water-solubility. PEG’s should be imitable by polyglyceryl and sugar derivatives but those haven’t usually been applied to pharmaceuticals yet… These synthetics are also more stable (less contamination) and usually inert. Me, I’d at least try vegetable oils too. Either alone or in combination with the aforementioned constituents.

More in a second post, this one is getting too long…

[Pharma]

Pure tocopherol and tocopherol acetate have the consistency of liquid honey, very viscous. If it’s more like syrup or even water, then it’s a dilution of some kind.

[Pharma]

Cyanocobalamine solution for injections are buffered although I don’t know the pH. Likely, the buffer is used for stability reasons and not to make the injection more comfortable since it’s one of the more painful injections and hence often combined with lidocaine.

According to MSDS, hydroxocobalamine is a stable compound, only contact with other heavy metals (than cobalt) and oxidising chemicals as well as light exposure have to be avoided. But information regarding this particular B12 derivative is incomplete. Cyanocobalamine has been better studied: mostly because of the cyano-complex, it is susceptible to light, temperature, air, humidity/water, bases, and strong oxidating agents. It’s pH in solution is about 6 which, as a rule of thumbs, is often the most stable pH. According to Wikipedia, it’s most stable between pH 4 and 6 and B12 solutions are said to be fairly susceptible to antioxidants such as ascorbic acid.

[Pharma]

Or bleaching products such as benzoyl peroxide .

Ascorbic acid may in fact cause bleaching but I don’t know how many % would have to be used to do the trick and I’m not sure if it also works on dark spots or just stains. I did manage to remove stains I got from handling colours and chemicals with the aid of ascorbyl palmitate but it took a lot and didn’t work as well as intended. Also, said spots were susceptible to decoloration by antioxidants.

[Pharma]

File is on its way .

[Pharma]

@Gunther 

Here’s how:

Weigh the beaker = tare weight. Add all the ingredients (without water) = total weight.

The amount (of water) to be added = tare weight + theoretical final weight - actual weight of beaker with ingredients.

[Pharma]

MarkBroussard said:

…but the conversion rate to free tocopherol when applied topically is at best 6%, so topically-applied tocopherol acetate isn’t really doing very much…

Ugh, that bad? Never paid any heed to that point. Thanks!

[Pharma]

Tocopheryl acetate is not an antioxidant and will not protect the product but become active only after penetrating skin and doing it’s work there. Tocopherol on the other hand is primarily used to protect the product from getting rancid and is usually not used as an active ingredient (unless tocopheryl acetate can not be used because it’s synthetic).

[Pharma]

I still measure them by weight.

If I don’t have their density and had to cook according to a recipe which only gives volumes: high-grade graduated cylinders are usually fairly accurate and can be used depending on required precision, whereas volumetric flasks and pipettes as well as syringes are more precise. But because volumetric flasks/pipettes are fixed volume and a PITA to clean and not suitable for viscous or hot liquids whilst syringes are usually fairly small, I still like going by weight no matter what.

[Pharma]

It depends on the used drug. Ointments show better occlusion and that’s about the only real difference. Because cutaneous resorption is usually only possible for lipophilic molecules, some oil as solvent may be advantageous. Also, many dermal preparations are meant to treat injured skin and that one often lacks it’s barrier function, an ointment is hence better suited than a light cream.

A different story would for example be salicylic acid or lidocaine: Both can be dissolved in water in their salt form but skin penetration of charged molecules (salts) is poor. Dissolving them in a polar oil seems logical but shows less effect/penetration than suspending them in mineral oil. The trick here is that oil-dissolved salicylic acid and lidocaine love being dissolved and hence stay in the solvent/oil rather than being pushed into the skin as it happens when using occlusive vaseline.

Besides, ointment isn’t usually used as scientific nomenclature and there’s a lot of mumbo-jumbo and marketing involved. An ointment might come as light cream, high internal phase oil in water emulsion, or as tough zinc oxide containing anhydrous salve. The pharmaceutical terms which describe the physical state and composition of the preparations aren’t usually what customer think it is.

[Pharma]

Regarding tackiness:

Quats (the standards are choline chloride and glycine betaine) and some organic acids such as citric and lactic acid tend to show strong melting point depression when mixed with urea or polyols. If the ratio is optimal, they form so called deep eutectic solvents which are usually of syrupy consistency. Take for example glucose and fructose, dissolved alone in water, they’re simply dissolved sugars but when mixed 1:1, they form artificial honey which does not dry out on your skin but remains tacky. The advantage is, that compounds can only penetrate skin when in liquid form and given that an eutectic mixture doesn’t dry out, it can fully absorb. The drawback is, that such a mixture remains tacky till it did whereas a “normal” dissolved salt will simply dry out and crystallize on the skin and therefore doesn’t feel tacky.

Multi-component mixtures are tricky to predict whether or not they show such an effect and it may appear only during the process of drying/resorption because composition changes when certain ingredients penetrate faster than others. NMF is such a mixture as well as nectar and honeydew… every plant knows how to concoct such deep eutectics whilst scientists just re-discovered them recently and still struggle do create mixtures of more than 3 components. BTW deep eutectis with urea render urea probably even more prone to hydrolysis…

[Pharma]

quote: Your short answer for now is accepted.

So, here’s the longer one:

quote: To make the buffer with the same 145.75 grams, it will be 145.75 grams
of Citric Acid monohydrate + 2247.1329 grams of Trisodium Citrate
dihydrate. Oh yea, 2.2471329 kilograms. This makes 84 M buffer.

No, not like that. Only 145 g citric acid and then adjust pH with some alkali. I was too lazy to calculate everything .

quote: I guess it is due to its high molecular weight compared to other salts
(Sodium Lactate is the worst offender in my case… I compared them and the
difference I noticed is their molecular weights.

And the fact that citric acid is a triple-acid. In most cases though, several charges on a molecule make things worse (e.g. bridging molecules and have them gel or precipitate). Lactic acid is fairly small and hence “hard” whereas citric acid has a larger surface and is hence rather “soft”. Each molecule has preferences for “hard” or “soft” partners (now I have to think of flowers and bees… I wonder why  o:) ).

quote: For example is from w/v% to mol/L and from mol/L to w/v%. There is a calculator for it but is a bit troublesome…

That’s why I created some excel files with all the stuff I have in stock and the needed formula.

quote: I see some use only ONE pKa of Citric Acid, there are also some use ALL
pKa of Citric Acid to do the calculation. However, majority agree to
pick the pKa nearest to the target pH that we want.

Depends on what you’re trying to achieve. If you’re simply trying to keep pH stable at about one of the pKa’s, than that one pKa is all you need because the other acid-parts will not budge (stay nearly fully protonated or deprotonated).

Buffer tables and calculations are only meant as estimate! pH depends and is affected by many things such as temperature, salt concentration… In the end, one tries to add just not enough of the acid or base (in your case NaOH), measureing pH and then slowly-slowly adding the remaining brine to bring pH up exactly to where it needs to be.

quote: It does not mention what sort of acid it is.

A buffer is as good as always composed of a strong acid and a weak base or vice versa. Mixing strong with strong will result in a salt; that’s why NaCl (table salt) has more or less no direct effect on pH. A mixture of weak/weak like ammonium acetate will result in a salt which can dissociate ammonia and acetic acid. It’s also not a good buffer because you have two “flexible” things. It’s better to have a “static” one as a constant/fixed point. If you take citric acid (weak acid) and add X parts of NaOH (strong base), X parts of the acid will be in salt form. If you added ammonia (weak base), it would be less than X parts because not just citric acid is buffering but ammonia too and it’s all wobbly-wobbly.

quote: Do you think humans are THAT consistent?

I had a customer at the pharmacy for whom I regularly mixed an OTC eye cream with additional 10% urea.

[Pharma]

@Dtdang

quote: our skin doesn’t absorb water? Only oils with small molecular weight can
be absorbed through our skin? Because Most active ingredients are water
soluble, therefore we need to choose oils(easy absorbed) and
emulsifiers with small molecular weight => cream is easy to absorb to
our skin?

It does absorb water in a way, just stay in the bath tub long enough and you’ll notice. Small molecular weight oils will absorb into the outer layer of the skin and will then get stuck. Small compounds follow certain rules (Lipinski’s rule of five) which aren’t a scientific fact but based on observation and originally made for orally available pharmaceutical drugs. Skin penetration is more regulated and hence, it’s rather a rule of three and/or a higher required lipophily. Though, too lipophilic (i.e. triglycerides) will have the molecule get stuck in the lipid layers of the skin because they completely lack water solubility and there’s quite a lot of water in our bodies. On the other hand, some molecules like heparin contradict all rules and still show transdermal bioavailability.

As mentioned by @ngarayeva001, some small molecules such as DMSO, laurocapram, urea, medium chain fatty acids, or isopropyl myristate may serve as resorption enhancers, rendering a cosmetic product into a pharmaceutical drug.

Furthermore, most creams aren’t absorbed but adsorbed. Although leaving a dry afterfeel, lipids stay on the skin often in a way like water in a sponge.

Which enhancer you want to use depends on the active ingredient. Too good a solvent will make the active stay in the solvent rather than going into the skin. Another consideration is that resorption enhancers aren’t necessarily solvents but usually show additional effects and may be chaotropic substances, cause swelling of the stratum corneum, and/or alter the lipid layer or intercellular protein organisation. All these effects reduce the skin’s protective function and make transcutaneous flux easier (some literature as example: CLICK ME). Again, it all depends on the compound you wanted to get through the skin.

[Pharma]

Maybe try searching under a synonym? Macrogoli 9 aether laurilicus (or laurilicum) and macrogol-6-laurylether

[Pharma]

Beakers aren’t meant to be precise. Use scales and take the marks for what they are, a rough idea . Etching can be done with hydrofluoric acid. Depending on where you live you may buy pens containing HF. Because it’s highly toxic it’s not readily available everywhere. Ask a glassblower.

[Pharma]

@Dtdang That’s ethanol, your cell gets drunk :smiley: . Naw, likely not drunk because that small quantity of ethanol gets fully metabolised.

[Pharma]

I wrote an article some time ago about silica. It’s not 100% what you’re asking for because the aim was to collect info on stabilised silicic acid. Still, it does cover the basics too.

I’m too lazy to re-write it just for you so I’d like to upload the file but it says that I’m not allowed to in this category. The text is also too long for a copy-paste ;( . If you’ve got an idea on how to solve the problem, I’d be happy to but till then…

[Pharma]

Here in Switzerland, you can get PhEur quality at every pharmacy. At least, they can easily organise it (50g, 250g or 500g).

[Pharma]

Become rich and famous and buy pre-made formulas @ Givaudan or Firmenich. They do everything for you except the marketing and sales . I don’t remember how many % of the perfumes on the European/US market sold by famous actors and the like were developed by Givaudan but it’s a major one.

[Pharma]

There’s a product line out there, called Mavena B12.

They originally tried to launch a pharmaceutical product for the Swiss market but were turned down by authorities (it was likely lobbying or some bureaucratic A-hole who didn’t like the idea of a cost-efficient vitamin cream helping sick people, don’t recall what exactly it was but it was some lame, bogus excuse). Hence, they started their business without the intended health claims in Germany and once established there could also sell in Switzerland (as a cosmetic product, not an OTC “drug”).

Innovative, nice product line-up, great results, probably not the soundest scientific foundation (not bad either, lower budgets have that side effect…). What’cha want more?

[Pharma]

40% ethanol make it self-preserving and there’s no need to add additional preservatives (except probably an antioxidant).

A spray for minor scratches? Ouch, that formula is going to hurt! Probably replace some of the ethanol with more glycerol? Even 10% ethanol are neither comfortable for scratches nor the best for a dry skin product IMHO.

[Pharma]

Just a short answer for now: It’s basically about the pH, not the amount of buffer. Go for pH +/-6.2 (that’s what we do in pharmaceutical preparations we make in the pharmacy). I don’t see a perfect solution for that problem (and I’m not the only one). I know of water-free formulations containing high amounts of urea which aren’t stable and science doesn’t really know why.

In my experience, mixtures of propylene glycol and urea are often tacky.

[Pharma]

TEA doesn’t “bind” but simply form a salt. “Binding” would imply a chemical reaction which would lead to amid-bond formation as for example with cocamide MEA ode DEA. This is not possible with TEA because that one is a tertiary amine, the amid would be positively charged and hence highly reactive. TEA simply abstracts a proton from an acid such as carbomer. Because TEA is not a very strong base, its salts and especially salts with weaker acids such as carbomer, free and protonated TEA are in equilibrium with each other, they form a buffer. Although the equilibrium is usually on the salt side, more or less free TEA is present depending on pH.

[Pharma]

Oh, BTW I forgot to mention: To do the whole thing buffered at pH 6.2, one would require 145.75 grams of citric acid and some base (I am to tired now to calculate how much alkali one would have to add in addition) to still end up with a pH of 7. Obviously, that wouldn’t fit into a 100 ml container, no would it?