Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: whitecoatblackhat on March 19, 2021, 09:17:57 AM
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Hello fellow chemists,
I'm looking for solvents that are capable of dissolving beta-sitosterol.
From what I read online, prior to purchasing the beta-sitosterol anhydrous powder, is that its solubility in ~100% ethanol is around 5-6mg per ml.
However, that's not the case.
I even tried dissolving as low as 0.5 mg of beta-sitosterol per ml of 99.8% ethanol and absolutely none of it dissolved.
I have certificates of analysis for both the beta-sitosterol and ethanol, so I'm certain that they are pure.
I'm aware that beta-sitosterol and all plant sterols are notoriously difficult to dissolve.
But still, I hope someone can maybe give a suggestion or some other helpful insight.
Every single response is highly highly appreciated!
Thanks!
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Its very lipophilic so DCM, toluene, EtOAc should be fine. Have you tried to heat the ethanol?
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Its very lipophilic so DCM, toluene, EtOAc should be fine. Have you tried to heat the ethanol?
Thanks for the reply rolnor! You always have fantastic advice!
I forgot to mention, that the solvent needs to be relatively skin-safe.
Because we'll be applying the solution to the scalp.
Hence, I can't really use any of these.
Also, heating the ethanol isn't really practical, as the beta-sitosterol will revert back to its insoluble state once the ethanol is at room temperature again.
That's why I'm looking for a skin-safe solvent that can dissolve beta sitosterol at room temperature.
I know, it's extremely difficult.
Could it be that somehow my ethanol isn't 99.8% but more 95-96%. I do have a certificate of analysis for that but I'm starting to doubt everything.
If the ethanol is 95-96% will these remaining ~4% of water interfere with the dissolving of beta-sitosterol?
Thanks!!!
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Some organics are very difficult and slow to dissolve. Heating up can speed up the process. Sonification can speed it up too.
Sometimes dissolving in one solvent and later mixing with another solvent can help.
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Some organics are very difficult and slow to dissolve. Heating up can speed up the process. Sonification can speed it up too.
Sometimes dissolving in one solvent and later mixing with another solvent can help.
Thanks for the reply!
Yeah, beta-sitosterol is surprisingly hydrophobic and extremely difficult to dissolve.
These are some great suggestions but I'm looking to achieve a long-term stable solution at room temperature.
Therefore, any temporary boost in solubility created by heat, sonification, etc. isn't what I'm after.
Mixing it with one solvent and then with another, isn't a problem.
I just need to find these hypothetical solvents.
Thank you so much
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Therefore, any temporary boost in solubility created by heat, sonification, etc. isn't what I'm after.
I think you are missing the point - these are not temporary boosts. These are way to speed up the dissolution. Chances are your problem is not that of the solubility being lower than reported, but that of very slow dissolution kinetics. If so, once you dissolve the sitosterol and prepare the saturated solution it should be stable.
I just need to find these hypothetical solvents.
That's where the rolnor's ideas can come handy, as with some luck in the final preparation concentration of solvents he suggested can be low enough to not be a problem.
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is it a powder or crystals? Crush as small as possible before mixing, and sonicate at say 40C. Maybe you could dissolve it in oil instead. olive oil for example, then apply to scalp.
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I think they use this as additive in cholesterol-lowering butter substitute so fatt, like oliv oil as suggested, could work fine.
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Therefore, any temporary boost in solubility created by heat, sonification, etc. isn't what I'm after.
I think you are missing the point - these are not temporary boosts. These are way to speed up the dissolution. Chances are your problem is not that of the solubility being lower than reported, but that of very slow dissolution kinetics. If so, once you dissolve the sitosterol and prepare the saturated solution it should be stable.
I just need to find these hypothetical solvents.
That's where the rolnor's ideas can come handy, as with some luck in the final preparation concentration of solvents he suggested can be low enough to not be a problem.
Thanks for the response.
Just now, I did try to dissolve 0.25% beta-sitosterol into 99.8% ethanol and heated up the ethanol until boiling.
Then used a high-powered immersion blender until it got fully dissolved.
So that worked as expected.
However, what also worked as expected is - I left the solution at room temperature and 4 hours later, I can see all the beta-sitosterol precipitate at the bottom.
So it definitely doesn't work that way.
This is only a temporary boost in solubility and isn't a long-term fix.
But thanks for the suggestions!
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is it a powder or crystals? Crush as small as possible before mixing, and sonicate at say 40C. Maybe you could dissolve it in oil instead. olive oil for example, then apply to scalp.
Hey, Thanks for the suggestion!
It's a very fine powder, not crystals.
I don't have access to a sonicator but I can buy one as long as I'm fully certain that it will help solubilize the beta-sitosterol.
Also, I did already try dissolving it in the purest, organic jojoba oil (for which I also have CoAs) and it didn't dissolve at all.
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I think they use this as additive in cholesterol-lowering butter substitute so fatt, like oliv oil as suggested, could work fine.
Yeah, it's a part of the E499 food additive.
But it doesn't solubilize in pure base oils. I have a lot of essential oils, maybe I can try them.
I also found that sulfobutyl beta-cyclodextrin helps solbulize cholesterol.
So, it might work for beta-sitosterol as well.
I'm just seeing some conflicting data regarding its skin safety profile.
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Therefore, any temporary boost in solubility created by heat, sonification, etc. isn't what I'm after.
I think you are missing the point - these are not temporary boosts. These are way to speed up the dissolution. Chances are your problem is not that of the solubility being lower than reported, but that of very slow dissolution kinetics. If so, once you dissolve the sitosterol and prepare the saturated solution it should be stable.
I just need to find these hypothetical solvents.
That's where the rolnor's ideas can come handy, as with some luck in the final preparation concentration of solvents he suggested can be low enough to not be a problem.
Thanks for the response.
Just now, I did try to dissolve 0.25% beta-sitosterol into 99.8% ethanol and heated up the ethanol until boiling.
Then used a high-powered immersion blender until it got fully dissolved.
So that worked as expected.
However, what also worked as expected is - I left the solution at room temperature and 4 hours later, I can see all the beta-sitosterol precipitate at the bottom.
So it definitely doesn't work that way.
This is only a temporary boost in solubility and isn't a long-term fix.
But thanks for the suggestions!
You may still have some dissolved even if you see some precipitates. You know for sure that the solution is saturated. Maybe try removing 10ml of the remaining solution and evaporate to dryness to see if there is still some dissolved.
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You could also try mixture of oil and ethanol.
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Because of the structural and solubility similarities of beta-sitosterol and vitamin D3, I would look into how VD3 is formulated for fortification of milk etc.
Note that for VD2 (not a typo) solutions are prepared commercially in propylene glycol or sesame oil.
Water-insoluble, anti-cancer drugs were/are dissolved in arachis oil for testing on rats.
If you were to get into the manufacturing phase, Note that elution of ortho-phenylphenol from silicone tubing by sulfonated cyclodextrin has been reported.
Regards,
MOTOBALL
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What about using something like limolene or related interesting smelling alkenes as a solvent? Citral is another. The class of chemicals is called terpenoids or isoprenoids. They are found in fruit, cosmetics, etc.
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You may still have some dissolved even if you see some precipitates. You know for sure that the solution is saturated. Maybe try removing 10ml of the remaining solution and evaporate to dryness to see if there is still some dissolved.
Thanks for the suggestion.
Yes, you're right. A small portion of the beta-sitosterol might be dissolved but it's too infinitesimal to make a difference.
I wanted to create at least a 0.5% - 1% solution and possibly 5% (but that's highly unlikely now).
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You could also try mixture of oil and ethanol.
Thanks for the suggestion rolnor!
I tried, it didn't work.
I tried alcohol, base oil, essential oil, polysorbate 20, 40 and 80, used PEG-40 Hydro. Cast. oil and none of these worked even in the slightest.
The only thing that works is heating the ethanol until boiling and then dissolving the beta-sitosterol with an immersion blender.
I'm able to create a 1% beta-sitosterol solution this way but it's only temporary. After 30 mins I'm starting to see precipitate.
Thanks!
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Because of the structural and solubility similarities of beta-sitosterol and vitamin D3, I would look into how VD3 is formulated for fortification of milk etc.
Note that for VD2 (not a typo) solutions are prepared commercially in propylene glycol or sesame oil.
Water-insoluble, anti-cancer drugs were/are dissolved in arachis oil for testing on rats.
If you were to get into the manufacturing phase, Note that elution of ortho-phenylphenol from silicone tubing by sulfonated cyclodextrin has been reported.
Regards,
MOTOBALL
Thanks MOTOBALL, really appreciate your response.
I wasn't aware of the D3 and beta-sitosterol similarities. I'll look into it.
On the other hand, because beta-sitosterol is structurally similar to cholesterol, I also found that sulfobutyl beta-cyclodextrin can possibly dissolve it.
So what I found coincides with your suggestion.
My manufacturer produces sulfobutyl beta-cyclodextrin, so I can try it.
The only unknowns are whether it's safe on the skin and whether it interferes with the transdermal absorption of beta-sitosterol.
Thanks!!
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What about using something like limolene or related interesting smelling alkenes as a solvent? Citral is another. The class of chemicals is called terpenoids or isoprenoids. They are found in fruit, cosmetics, etc.
Thanks for the response. Much appreciated!
I assume you mean limonene, not limolene?
They are found in essential oils. Limonene especially in grapefruit EO (or other citrus EOs).
I did try essential oils to solubilize beta-sitosterol and it didn't work.
Also, limonene seems to be a PGE2 antagonist and I'm trying to avoid that in the context of hair growth.
Thanks!
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Can you use surfactants to keep it in the ethanol?
You've got a tough customer on your hands! I've never personally found any small molecules that, in an emergency, didn't have some solubility in hot DMSO, but clearly that's out of the picture.
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Have you tried to dissolve it in varm vegetable oil? You can heat to 100°C or even more.
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Can you use surfactants to keep it in the ethanol?
You've got a tough customer on your hands! I've never personally found any small molecules that, in an emergency, didn't have some solubility in hot DMSO, but clearly that's out of the picture.
Yeah! I agree. Thanks for the suggestion.
As I mentioned in one of my above posts, I did try using surfactants to create some sort of an ethanol beta-sitosterol emulsion.
I used all the polysorbates/tweens and also PEG-40 hydrogenated castor oil.
Nothing worked.
As for DMSO, yeah. It's probably the most insane permeation enhancer and solubilizer ever.
I've heard anecdotes of people pouring a cup of strawberry juice, then rubbing their finger in DMSO and sticking it in the cup, which made them "taste" the strawberry juice through their finger.
That's how much it allows stuff to pass through the SC.
It's totally unscientific and anecdotal but it's still interesting to hear stories like that.
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Have you tried to dissolve it in varm vegetable oil? You can heat to 100°C or even more.
Thanks for the suggestion!
Yes, I tried dissolving it in both cold and hot jojoba oil, olive oil, safflower oil and sunflower oil.
Nothing worked.
Beta-sitosterol is one of the toughest organic compounds, I've ever worked with.
Even if I did get it to dissolve somehow. The entire solution must be optimised for beta-sitosterol.
I won't be able to put other compounds in it. Which makes me more and more reluctant to continue pursuing this thing.
I'm looking into other things now, such as ketoconazole (in the context of hair loss prevention/hair growth).
Thanks!
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One method of trying to improve solubility is co-crystallization. Maybe you could search the literature for your compound and see if there are any (safe) coformers it likes. There are methods of cocrystalization that can be done without solubilization such as liquid assisted grinding. Add the coformers at the specific molar ratio, add a drop or two of solvent and grind them together. Or you can slurry them by stirring the coformers over night in solvent. The resulting cocrystal may be more soluble than the single compound and dissolve more readily in the solvents you've already tried.
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One method of trying to improve solubility is co-crystallization. Maybe you could search the literature for your compound and see if there are any (safe) coformers it likes. There are methods of cocrystalization that can be done without solubilization such as liquid assisted grinding. Add the coformers at the specific molar ratio, add a drop or two of solvent and grind them together. Or you can slurry them by stirring the coformers over night in solvent. The resulting cocrystal may be more soluble than the single compound and dissolve more readily in the solvents you've already tried.
That's brilliant. Thanks a lot, I'll definitely look into co-crystalization.