[Pharma]

Finally, here’s the formula part:
1 urea gives 2 ammonia and one citric acid captures up to 3 ammonia. We neglect pH here, else it would be a mix of 8 citric acid to 92 citrate at pH 6.2 resulting in ~50% hydrogencitrate and ~50% citrate. Simply said, max 50% of the added acid would be able to capture a single ammonium before the buffer is used up completely. Notably, a triple acid makes calculations VERY difficult, so difficult that either programs are used to predict things or people go with tables/graphs based on measured values (I did exactly that) and estimate from there.
No offence, but for you, I go with the simple stuff because calculating is useless anyway:
Urea has a molecular weight of 60.06 g/mol and citric acid monohydrate (to usual form) of 210.14 g/mol. “g/mol” is a measure of grams per a certain number of atoms. We could also work with molal which reflects the amount of acid/base moieties per molecule but that’s confusing and doing a rule of three as follows is easier.
We want to know how many grams of urea correspond to how many grams of citric acid: 1/60.06*210.14=3.5 (rounded)
3 urea = 6 ammonia = 2 citric acids molecules: 3.5/3*2=2 2/3
In a 5% urea preparation of 100g are obviously 5 g urea and therefore 11.66 g of citric acid would be required. Your starting solution would be at pH ~1.5 and at the end of full degradation around pH 7 (neutral because triammonium citrate is “self-buffering”).
Now that you know why you don’t need that much buffer but rather a stable product to start with, this huge quantity of citric acid doesn’t just sound stupid from a cosmetic point of view.

I hope you enjoyed the good night story and learned something useful today.
Greez!

[Pharma]

@Cst4Ms4Tmps4 Okayokay, I’ll do it… but first some digression (to build up suspense and trying to give you an understandable picture of the processes involved and why that formula isn’t really helpful).

Imagine you’re having a party (your product) on a flower field (your vessel). On there are people (water molecules) and bee hives (urea). You’re playing music (pH) and the people have fun and are dancing around. Obviously, sooner or later, someone stumbles against a hive and the bees (ammonia) start swarming (urea gets degraded). The more bees flying around, the more people start panicking, knocking over more bee hives… and before you know it, the party’s over (your product is toast).

In order to protect people from bees or vice versa, you could physically separate them like I mentioned in an earlier post about corn starch. Unfortunately, bees like flowers (urea is super water soluble)…

Another option is to calm the people by bringing acid to the party (lower the pH) and avoid playing heavy metal (high pH) which would have them pogo dancing and knocking over the hive even faster. Too bad that acid will render the bees quite sensitive, having them swarm out at the lightest knock against their home. The perfect balance would be pH 6.2 as for example recommended by the DAB/NRF (German guideline for pharmaceutical preparations).

An important point in an earlier post is water activity. Sadly, it got more or less completely ignored. Water activity is as follows: Take a glass of tap water (full water activity) and pour it over your head . Now, take some ice (frozen water has nearly zero water activity) and try to get wet: even an iceberg the size which could sink a Titanic wouldn’t work. Surely, a cream doesn’t contain ice unless it’s ice cream but by adding solutes, the water molecules gain order and form sort of a liquid crystal structure. It’s like inviting a few singing hippie girls (solutes such as lactate salts) to your party. People around them will gather together, holding hands and listening. These flocks around your flower power girls aren’t static, people still move a bit, can change hands, join or leave the groups. The more girls there are, the less people are wandering around and stumbling against the bee hives, water activity drops and the party gets more stable.

Still, it will never be at a point where there are no disturbed bees unless you don’t invite people (avoid water completely). Therefore, you hang out some glue traps (use a buffer). As you can see, there’s no need to distribute one trap for every bee. Besides, and that’s probably the more important point, hives/urea does not just decompose to bees/ammonia but also to carbon dioxide, a gas… errr…. let’s call it bee farts. A glue trap might catch the bees but won’t prevent them from letting a last fart.

In theory, carbon dioxide (CO2) reacts with water to form carbonic acid and that one reacts with two ammonia to form ammonium carbonate -> problem solved, everything neutralised. Too bad that only ammonia is well water soluble, CO2 on the other hand is very slow to react with water and gasses off. As a rule of thumbs, a gas has a 1’000 times greater volume than a solid. In other words, if 0.1% urea in a 5% urea solution degrades, the volume increases by 5% (5 ml in a 100 ml tube). The resulting foam or bubbles will be noticeable and increases pressure enough to turn your product unsellable. Therefore, the human body uses carboanhydratase, an enzyme which catalyses (speeds up) the conversion from CO2 to carbonic acid and vice versa. Without it, you would be dead within 1-2 minutes. Synthetic catalysts doing the same job aren’t, for many reasons, suitable for cosmetic preparations. This means that there’s no way of getting rid of CO2 gas. It also means that the very small quantity of ammonia which might appear before your product explodes (a fully degraded 5% urea solution would turn a 100 ml tube into a 5 litre balloon) is very easily buffered away, likely by also present salicylic acid (bar tenders) which are poorly water soluble but dissolve well in alcohol(ics). Alcoholics form similar flocks around them like the other people around the hippie girls. Still, there will be enough salicylic acid available to catch all ammonia (bar tenders are great with fly swatters). Now, why doesn’t adding salicylic acid suffice? Because for one, it’s an acid and hence probably too much (see above), and for another, it means that water activity is VERY important, probably more so than anything else. Adding acid or a buffer (the acid part of it) just keeps degradation from speeding up but not from happening in the first place.

Patience, we’re getting there… slowly…

In order to be able to calculate things, you have to know that it’s only a 1+1=2 on paper or if pH doesn’t matter. As soon as you require a certain pH or pH range, buffers become important. Well, in creams and the like, there’s often enough inherent buffering capacity to do the trick in everyday stuff. A buffer works by catching acids and bases alike without changing pH too much. This effect is only apparent within +/- 1 unit around the pKa for acids and pKb for bases. Every acid or acid moiety has a pKa (i.e. citric acid has 3) which is a constant: It means if pH equals pKa, half the acid is in acid form (protonated), half in salt form (deprotonated). Shifting pH by 1 unit changes the 1:1 ratio by a factor of 10. In case of lactic acid where the pKa is 3.8, at a pH of 4.8 1 part will be in acid form and 10 parts will be in salt form. At pH of 5.8 it’s 1:100 and at pH 6.8 1:1’000. Urea is most stable at pH 6.2 or at 1 lactic acid to 250 lactate. In other words, only 0.4% of the added lactic acid buffer are available for capturing ammonia (on the other hand, the whole rest would neutralise an added acid). Theoretically, lactic acid is a useless buffer for a pH 6.2. Also, lactic acid is less acidic than salicylic acid and hence, the buffer composition of a mix of salicylic acid plus lactic acid-lactate buffer will in reality be comprised of lactic acid and salicylate (mostly just salicylate) unless a lot of non-aqueous liquid is added to shift equilibrium and pKa values (which are solvent dependent).

If you still wonder (you still with me?) why adding lactic acid-lactate buffer does work: It’s not about the buffering (capturing ammonia), it’s merely the pH (and that one won’t really change before the bottle explodes) and water activity (cause lactic acid and lactate are good in lowering water activity).

Got the picture?

(Your post is too long, more in a second one.)

[Pharma]

@Dtdang Ascorbic acid is not just an antioxidant (a reducing agent) but also a so called conjugated acid. The hydroxy group(-s) responsible for both actions can either be esterified with ethanol or with a carboxylic acids forming a fairly stable acid anhydride. This feature is quite exceptional but way off the point .

Anyway: Such a modified ascorbic acid is no longer acidic nor an antioxidant, it’s “dormant” and doesn’t degrade or react before reaching the interior of a cell. Once inside a cell (the modification makes it lipophilic, oil-soluble and hence cell permeable) it meets different enzymes, mostly lipases, which cleave off the protecting group liberating active ascorbic acid which becomes trapped within the cell where it can work its magic.

Retinol profits from the antioxidants which render it more stable. Else, there shouldn’t be any negative interactions.

[Pharma]

Preservatives in above products are:

1: Glyceryl Caprylate, Sodium Levulinate, Sodium Anisate

2: Salix Alba (Willow) Bark Extract, Leuconostoc/Radish Root Ferment Filtrate

3: Leuconostoc Ferment Filtrate, Propanediol, Phenethyl Alcohol

These are natural or semi-synthetic but from renewable resources. There’s probably no THE best preservative which fits ’em all but a range to choose from. Cosphatec for example has a nice pdf available with different blends for different applications.

[Pharma]

Lipophilic ascorbic acid derivatives such as ascorbyl palmitate, tetrahexyldecyl ascorbate and also ethyl ascorbic acid penetrate skin better/deeper than pure ascorbic acid. In addition, the latter two are without charge and are “inactive”, they require activation by cellular enzymes to become active vitamin c and are therefore said to be superior for above application. I have zero experience with ethyl ascorbic acid and only a scientific one regarding ascorbyl palmitate (I love that stuff!). Theoretically, ethyl ascorbic acid should not interfere with anything in a cosmetic preparation, is the smallest molecule of all the “prodrug” derivatives and hence, in theory, the best of ’em all .

[Pharma]

@Cst4Ms4Tmps4 By using molecular weights.

But don’t forget: this is cosmetics, not exact science and there’s no real use for such a calculation . If you want to mix a buffer, go with a buffer table and use a pH meter (that’s also what scientists do first). If you want to add a preventive buffering (“quenching” would be a better word) system, you may want to go with something that shows additional effects and simply add “enough” if them. Here’s a little list of such “double-edged” ingredients:

- Lactic and pyroglutamic acid and their salts are humectants

- Citric and phytic acid and their salts are sequestrants

- Anisic, levulinic, and benzoic acid and their salts are preservatives

Use a mixture of two, three or even more and chances are that you get a product which is buffered over a broad pH range. Simply adjust the final product to the desired pH and you’re (probably/hopefully) good to go.

That would be my advice and it would still be my advice even if you were a rocket scientist .

[Pharma]

Ups, sorry, my bad. I was mentally at triethylamine instead of triethanolamine.

The latter has (I did have to look it up, I admit) a melting point around room temperature and simply heating it a little bit will re-liquefy everything and you’re good to go. Even taking the supernatant would work but is likely to contain more impurities than the crystals. Re-crystallisation cycles are used to purify different things .

Is it still useful after all this years? Running some purity tests would help…

[Pharma]

TEA doesn’t crystallise. If there’s crystals inside, it’s not TEA but probably a degradation product or something else entirely.

[Pharma]

Darn, it made a smiley out of my D doublepoint

[Pharma]

@johnb Allegedly, it’s the pH but honestly, lactate buffer has its upper limit at pH ~5. Hence, choosing lactic acid-lactate at pH 5-6 to stabilise a solution from getting alkaline sounds completely stupid (nevertheless, it’s used in different Eucerin products… LoL).

@Cst4Ms4Tmps4 Temperature is always sort of an issue with organic buffers because they change pH with temperature .

As a rule of thumbs:

A: Add enough to capture all the extra acid/base you expect to appear.

B: If you need more than 10 % of the compound you want to buffer, try other options. Correctly, it’s % molal but being a rough estimate, % weight does just fine.

C: There’s always a formula to calculate stuff. The rule is simple: 2 lactic acid molecules capture 1 degraded urea, 2 citric acid molecules capture 3 degraded ureas. Though, you don’t need to capture 100% of the urea but just trace amounts which would otherwise rise pH and cause exponential urea degradation/pH-rise. If you need a lot, than your urea preparation is so unstable that you should reconsider your formulation.

Every buffer has it’s range. If you expect a pH rise, you should opt for one which has it’s pKa at or less than 1 unit (+0,5 would be perfect) above the desired pH of your preparation. This way, you have between 50 and 90% of the added buffer really acting as buffer and get the most out of it without actual pH changes.

@Theotherusers Read something about a company which sprays aqueous urea solution on corn starch and let it dry. Urea crystals form within the starch and can then safely be used in their creams.

[Pharma]

First: I don’t speak from experience regarding arbutin in cosmetics but from experience as a pharmacist with a PhD in pharmacognosy/phytochemistry: keep in mind that some things are true for both, others are quite different between scientific lab-work and real life .

Arbutin will hydrolyse under acidic conditions to form glucose and the more reactive hydroquinone especially at elevated temperatures. Arbutin and even more so hydroquinone are susceptible to oxidation (benzoquinone is formed) already under slightly alkaline conditions and/or UV irradiation which cause their degradation sometimes within minutes to form a dark coloured polymeric substance. This effect is pronounced when nucleophilic substances such as thiols (e.g. cysteine) and to a lesser extent primary amines (rare in cosmetics) and even certain alcohols (abundant in cosmetics) are present.

A slightly acidic environment (pH about 5-6) and room temperature keeps the hydroquinone moiety safe from degradation and isn’t too acidic to cause arbutin hydrolysis but acidic enough to prevent chemical reactions with other ingredients.

A problem with hydroquinone can be that it may start an autocatalytic oxidation of itself and of ascorbic acid if the latter is present at active concentrations (>1%) rather than just as antioxidant for “preservation” (~0.1-0.2%). Mind, arbutin & high ascorbic acid is a common skin bleaching combination. The phenomenon of hydroquinone and ascorbic acid degradation isn’t always predictable but can cause dark colours either homogeneously throughout the product or as spotty/patchy appearance due to the vicious cycle randomly starting in just a few places where by bad luck the reaction is kicked off. This reaction is again pronounced under high temperature, high alkalinity and UV-irradiation and “gets exponential” when (pro-)oxidants such as benzoyl peroxide or heavy metal ions for example from iron oxides are present. Notably, this degradation requires oxygen! EDTA and other strong metal chelates can help dealing with trace amounts of iron and vacuum-mixing and a non-transparent, airless pump dispenser should be of great advantage too. But sadly, the developing colour is visible at really low amounts and completely avoiding oxygen is nearly impossible. Avoiding susceptible ingredient combinations would be the better way to go.

Besides: A proper ingredient listing of your spotty product might shed more light on your issue .

F*** errr… EDIT: Today isn’t my best day ;( . I just realised that I misunderstood your question and wrote the whole thing in vain .

Here’s the useful part: Experience in the pharmacy with dark spots says that arbutin alone doesn’t suffice. Combinations of hydroquinone with other things might but therein it’s unpredictable to know which ingredient does what and to which extent. Besides, hydroquinone is skin permeable and “bleaches” whereas arbutin is said to inhibit melatonin formation and is very unlikely to reach high enough concentrations in the deeper areas of the skin where true pigment spots are produced.

[Pharma]

Or use creatine ethyl ester hydrochloride or creatinol-O-phosphate .

[Pharma]

In my experience, most people don’t even know the difference nor care that there is a slight one (even in scientific publications!).

Most creatine sold is actually creatine monohydrate . Once you put anhydrous creatine in water it will “hydrate”, resulting in the exact same thing if you consider the slight difference in molecular weight of the two.

I got my creatine from one of the many “body-building webshops”… again, most sell monohydrate even if that’s nowhere mentioned.

[Pharma]

Reformulating your question wouldn’t be the worst thing to do . Nonetheless, different stuff which keeps your skin moist also keeps the product ‘wet’ .
You might try to add something hygroscopic (stuff/chemicals which attract water), often called moisturising agent. NMF (natural moisturising factor, it’s a blend), glycerol, glycols, and other polyols such as sorbitol, PCA, ectoin etc. are examples.

[Pharma]

Are you sure this formula contains micelles? I can’t say I’m 100% sure but I would guess that PEG-6 caprylic/capric glycerides and cetrimonium chloride won’t form micelles (besides that, there’s nothing else in it which would even remotely participate in micelles).
The salts might be in there because the formulator attributes some effect beyond galenic/cosmetic formulation and rheology? Or it’s there to adjust osmolarity in order to avoid a burning sensation when getting into eyes and mouth?

[Pharma]

You could also use glycerol… With regard to formulations, one could say it’s the grandfather of glycols although IMHO it’s inferior in many regards. To my knowledge, there are no real alternatives which cover all aspects and advantages of glycols. Though, depending on what you want to do with them or which of their activities/effects you want to mimic, you should be able to find natural (i.e. commonly found in nature) replacements. Like urea, glycerol, PCA, NMF and the like as moisturiser/humectant or glycerol and ethanol for their self-preservating and co-solvation effects (at high enough concentrations). But the skin feeling and texture etc. won’t be the same.

Besides, that something is natural derived (i.e. from a renewable, non-petrochemical source) does neither mean it’s “natural”, that the synthesis employed is “green”, nor that the product is eco-friendly and bio-degradable . True, in case of propylene glycols, at least the latter two are true.
Glycols are rarely found in nature but the simple structure especially of propylene glycols (i.e. 1,2- and more so 1,3-propanediol) makes it very likely (I have to admit, I do not know for certain but think that it actually is the case) that these do indeed occur as side products in trace amounts for example in natural microbial metabolism. Propanediols produced on an industrial level by fermentation isn’t exactly natural; from what I understand, DuPont for example uses genetically modified microorganisms for this process like elaborated for example in this publication http://www.ncbi.nlm.nih.gov/pubmed/9496676

[Pharma]

Glutathione doesn’t penetrate into the skin (unless you use fancy-shmancy hightech stuff). It is also highly susceptible to oxidation (the reduced, active form) and will degrade very fast once put into solution. It’s just an expensive claim ingredient .
If you want something similar with a slightly increased availability (though not much), go with N-acetylcysteine. It is the protected and hence more lipophilic part of glutathione which makes it a good antioxidant and anti-aging product. If you added glycine and glutamic acid at equal molare ratios, you could claim that your product contains the building blocks of glutathione and that the skin will form it (which is true, on a theoretical and/or in vitro level)…

[Pharma]

Thanks for the brain food!
Though, a polymer and especially one which isn’t highly water soluble is a no-go for me (although it might result in a better depot effect) but I like your idea of a self-emulsifying system. Applying something like a liquid crystal structure on plants is… I don’t know. Which gets me intrigued . Alkylpolyglucosides such as contained in Montanov 68 are already used on plants with good success due an optimal surface tension. The rather low HLB of the liquid crystal emulsifiers, though rather irrelevant regarding stability, bothers me a bit; I want that tria to diffuse out of there and into the plant; less ‘likeliness’ might be preferable.

Thanks to you two I just realised that I don’t know how and where exactly triacontanol acts on plants and this point is likely the key to success. Is it sufficient to penetrate the cuticle (-> Olivem 1000) or does it need to enter through the stomata (-> Micro-/nanoemulsion) like most ‘foliar feeds’?
Please keep the ideas coming! It works!

[Pharma]

Thanks for you input!
I’m not really well equipped right now but I have ultrasound and can improvise.
Any suggestions for a formulation which might tolerate a high percentage of triacontanol?

[Pharma]

You should drink some of it… the Epsom salt will certainly help you to get an ‘excuse’ to stay at home.

[Pharma]

He sure does. That community uses more than just triacontanol to boost yields .

BTW I know that music can be inspiring but that wasn’t what I was looking for LoL.

[Pharma]

Forgot to say:
The stock ‘solution’ should, for practical reasons, contain about 1% triacontanol, and has to be stable.
This will be diluted 1’000 times in water and sprayed on plants or diluted 100 times and used for irrigation. This solution should be stable for at least a day, longer would be better.

[Pharma]

Cool!
Good luck and I’m looking forward to whatever you learn!

[Pharma]

@Bob Thanks for the flowers <3
Although, I’m usually quite serious and… (add pretext and other excuses HERE)

[Pharma]

Interesting! Thanks for sharing!

That’s a lot of phytic acid; it will likely ‘overpower’ the chitosan molecules and reduce their gelling efficacy and avoid cross-linking but that remains to be tested. How much chitosan would you want to include anyway?

Does your clay help with stability (except making things thicker), like thixotropy as seen with bentonite? If not, then that’s a good sign that it could tolerate chitosan quite well. A low CEC means that just a little chitosan could neutralise the surface charge and completely change the physical/rheological behaviour of those particles.

The zeta potential is a measure to predict stability of emulsions and suspensions based on their surface charge. I usually use magnets to explain it but as we’re already into the dirty talk (I honestly wasn’t thinking what you’re thinking but now that you mention it ROFLMAO): Imagine you were in a bar with only women, all heterosexual. The more hetero you are, the more you will repel each other and there less cuddling (aggregation) or even *cough-cough* (coalescence) there will be, the room will remain in order, the atmosphere stable. If you now add some chippendales (opposite charge) all hell will break loose…
In case of non-ionic particles or surfactants (-> PEGs) it’s more like you being in a lesbian bar: The more and longer arms and legs you have and the wilder you wiggle them around, the higher your chances of keeping the hot chicks off of your skin. I hope you get the point .

Bottom line is: I suppose there’s no other way than to try.