Experiments in dissolving spironolactone... (Part 1)

[Bryan]

This is a re-post of something I originally posted almost exactly three years ago. Since there's been a lot of discussion by "college" lately on the nitty-gritty details on mixing your own topicals, I thought he might find all this somewhat interesting.
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I know that some of you make your own spironolactone topicals (either solutions or creams), so the following should be very relevant and comforting for you do-it-yourselfers!

Even though I also make some of my own topical concoctions, I've always felt slightly uneasy about the general technique of crushing-up spironolactone tablets and mixing them in with Rogaine or other topical vehicles. Does the spironolactone REALLY get dissolved into the alcohol, or does it just stay behind in all that sediment which falls to the bottom of the bottle? I finally decided to put that to the test, and the results appear to be an unequivocal and SPECTACULAR success! Here's a brief outline of what I did, and afterwards I'll even go into a little more detail by posting the actual numbers I got:

I've previously posted that I use generic spironolactone tablets ("Spirotone" brand) which contain 100 mg of spironolactone each. The tablets themselves weigh 500 mg, so that means that they must contain 100 mg of the active drug and 400 mg of inert tablet fillers and excipients (that's what _apparently_ forms that messy sludge which refuses to dissolve in alcohol!). I took one Spirotone tablet and finely powdered it in a mortar and pestle, just to make sure that every bit of the spironolactone in it would dissolve (assuming it was going to dissolve, of course) in the next step. I dumped the tablet powder into a small glass vial of known weight. Measuring the weight of the vial + powder, I verified the exact mass of the powder sitting at the bottom.

Next I added about 12 mL of pure Everclear, enough to be sure that it could completely dissolve all the spironolactone in that powdered tablet (assuming that it was in fact going to dissolve, of course...I pre-calculated that the concentration of spironolactone in the Everclear would be around the 1% level, which I figured it should easily be able to hold). I capped the vial and THOROUGHLY shook it over an extended period of time to be CERTAIN that the alcohol in the Everclear would completely dissolve whatever it was going to dissolve. Then I set the vial down in a cool, dark place to let the undissolved sediment slowly settle to the bottom of the vial.

24 hours later, it had settled-out nicely, leaving a pale yellow liquid (Everclear and whatever solute it contained) sitting over a milky-looking sediment. Next came the tricky and tedious part: I sat down with a long, slender glass eyedropper with a narrow tip at the end and SLOWLY and CAREFULLY removed as much of that Everclear above the sediment as I could. I did it without moving or jostling the vial, so that the sediment wouldn't get stirred-up and withdrawn by accident, along with the liquid. It took me about 45 minutes of tedious effort to do that (with beads of sweat popping out on my forehead), but I got rid of just about every last bit of liquid that I safely could (about 96% of the liquid, as I was able to calculate later). This left only the sediment lying in the bottom of the vial, which was still wet with a little remaining Everclear. I set the vial out to air-dry the rest of the way by itself.

Two days later it was completely bone-dry, with just the sediment remaining in the vial. And here came the CRITICAL STEP: I weighed the vial and its contents for one last time, and it was EXACTLY 400 mg higher than the empty starting weight of the vial!! It was "dead nuts", to use the technical term! That proved beyond any reasonable doubt that the Everclear did in fact dissolve all 100 mg of the spironolactone in the crushed-up tablet, and left behind all 400 mg of the fillers and excipients (BTW, this also demonstrates a simple way to remove all that sediment: just remove the good spironolactone-containing liquid with an eyedropper, and discard the remaining junk). I was _thrilled_ to be able to satisfy for myself that the fundamental process that we've been using with spironolactone tablets is sound. Further experiments I'll be doing (Part 2) will try to determine the maximum concentration of spironolactone that can be achieved with Everclear and Everclear/PPG mixtures. Stay tuned.

For those of you who want to see the actual numbers I got in my little test to double-check my method, here they are, straight out of my notes:

Mass of empty glass vial: 11.88 grams

Mass of vial + crushed spironolactone tab: 12.39 grams (my scale is accurate to +/- 0.01 grams)

Mass of vial + tab + Everclear: 21.94 grams

(After removing liquid and drying for two days)
Mass of vial + sediment: 12.28 grams

There ya have it: 12.28 - 11.88 = exactly 0.4 grams (400 mg) of sediment. Yes, I was as astonished as the rest of you to see it work out EXACTLY like that, to within the accuracy of the scale itself. I almost fell off the chair when I saw that!

Bryan

 

[Mer]

Thank You,

That's excellent Bryan.

Mer

 

[CCS]

I'm not convinced by that experiment. The exactness of the 400mg is compelling, but I need to see what the inactive ingredients are. If there is any lactose in it, that would dissolve in ethanol, and compete with the spironolactone for solubility. Also, if you got only 96% of the liquid, that means 4mg of spironolactone should have been left in the vail after drying, so it should have been 404mg, not 400. While the 400mg sounds like it can't be coincidence, I think the fact is should have been 404 discredits that number a bit, and tells me at least 4mg of something else was dissolved too.

90% everclear of the 75%? I would like to use 70% isopropyl alcohol because it is cheap. While the water should hurt spironolactone solubility, the longer carbon chain should help it. Anyone know if isopropyl alcohol could harm hair, compared to ethyl alcohol? I can get ethyl alcohol denatured with methanol cheaply, but I'd rather risk a high concentration of isopropyl than a low concentraiton of the methanol.

Spirotone. I'm going to find out if that is cheaper than spironolactone.

 

[Bryan]

I'm not convinced by that experiment. The exactness of the 400mg is compelling, but I need to see what the inactive ingredients are.

I did a Google search on "Spirotone", and the first link contains the following information:

"Each SPIROTONE tablet also contains quinoline yellow, sunset yellow, erythrosine, polysorbate, peppermint oil, povidone, microcrystalline cellulose, maize starch, sodium starch glycollate, talc, magnesium stearate and lactose."

If there is any lactose in it, that would dissolve in ethanol, and compete with the spironolactone for solubility.

There's lactose in it, but lactose is practically insoluble in ethanol, and I imagine the cellulose and the other starchy materials are, too.

Also, if you got only 96% of the liquid, that means 4mg of spironolactone should have been left in the vail after drying, so it should have been 404mg, not 400. While the 400mg sounds like it can't be coincidence, I think the fact is should have been 404 discredits that number a bit, and tells me at least 4mg of something else was dissolved too.

I didn't intend to make THAT big a deal out of the fact that I got exactly 400 mg. I just found it highly amusing that it turned out that way. Rather poetic, in other words! :wink:

I'm sure there was actually a SMALL amount of spironolactone remaining in the sediment from that bit of liquid which I wasn't able to remove, and a SMALL amount of certain other solutes in the ethanol, along with the spironolactone. But I still consider that to be rather persuasive circumstantial evidence that the great majority of the spironolactone was indeed getting dissolved.

90% everclear of the 75%?

95% Everclear. 190 proof.

Spirotone. I'm going to find out if that is cheaper than spironolactone.

Being a generic, it's definitely cheaper.

Bryan

 

[CCS]

Bryan (or anyone using spironolactone tablets),

Does home made spironolactone stink if you are not using minoxidil?

Also, does PPG dissolve a lot of the tablet, or mostly just the spironolactone?

Bryan, do you know if PPG can make a 4% spironolactone solution?
I ask because I want to dissolve just spironolactone out of a tablet and make my own cream by adding other stuff to it, but with 1% ethanol, that would mean a 0.3% spironolactone solution if the cream is 1/3 ethanol. I want a 1-3% spironolactone solution, and want to use 20-30% PPG.


I want my final cream to be

2% spironolactone
20% tap water
25% ethanol
25% PPG
20% fatty acids (with maybe some glycerol in them)
7% oil from safflower, borage, and flax, maybe some glycerol
1% Dr Proctor's NANO shampoo (emulsifier, if needed)

I realize it would be a lot easier to just make an RU cream. It would also be easier to use with minoxidil. If I knew the RU would not react, I'd make this cream with my minoxidil. That would be nice, for fewer applications per day. But how to know if RU will react with minoxidil...

I'd prefer spironolactone because if castration won't regrow hair, then I'd rather spend that money on Dr Proctor's SODs. I just would like to know how to keep spironolactone from reacting with minoxidil so I don't have to space out 4 applications per day.

 

[Follically Challenged]

It'd be easier to use a coffee filter to separate the spironolactone solution from the gunk.

 

[CCS]

the spironolactone settles out. That is not the problem. the problem is dissolving all the spironolactone. i don't know how soluble it is. if I must use enough ethanol to to a 1% solution, then any cream I make from that will be less than 1% spironolactone. I don't want to evaporate the spironolactone either. I was hoping the PPG would dissolve a higher percent, but I don't want it dissolving the filler. If it does dissolve some of the filler, the filler that is dissolved will pass through the coffee filter.

 

[Follically Challenged]

I was saying that to Bryan about the coffee filters.

Do you think spironolactone would be that hard to dissolve? I wonder what the Merck Index has to say about Spironolactone.

 

[CCS]

can you find a merk index online? I guess I could just go to the science library.

yeah, Bryan could save time with the coffee filter. but he does not need it for the filler to settle out.

 

[CCS]

I read on HLH that spironolactone is most stable at a pH of 4.5. Appearantly a lot more people on that site like to mix up there own stuff. Citric acid can help get that pH, though I think fatty acids are near that pH too. They are half dissociated at pH 5. Anyway, if you use the wrong pH, the spironolactone breaks down faster and smells.

There was an error on the site, though. It said citric acid salts would give a pH of 4.5. The truth is once the metal ion leaves, the citrate would pull a proton out of solution, and give a pH above 7.


topical spironolactone, according to lee, turns skin testosterone into estrogen.

 

[Old Baldy]

I read on HLH that spironolactone is most stable at a pH of 4.5. Appearantly a lot more people on that site like to mix up there own stuff. Citric acid can help get that pH, though I think fatty acids are near that pH too. They are half dissociated at pH 5. Anyway, if you use the wrong pH, the spironolactone breaks down faster and smells.

There was an error on the site, though. It said citric acid salts would give a pH of 4.5. The truth is once the metal ion leaves, the citrate would pull a proton out of solution, and give a pH above 7.


topical spironolactone, according to lee, turns skin testosterone into estrogen.

FWIW I use citric acid to lower ph. Alot of guys use vinegar.

Adding EDTA will chelate the metal ions and prevent them from separating. Add EDTA first then add the acids.

 

[CCS]

EDTA attaches to metal ions, engulfing them. That will keep them from re-combining with the deprotonated acid.

If EDTA helps, it is because it is a 6 proton acid and will send off a few protons to lower the pH of the solution, negating the need for the salt.

thanks for the vinegar idea. i wonder if there is any way I could use vitamin C as my acid.

 

[Old Baldy]

EDTA attaches to metal ions, engulfing them. That will keep them from re-combining with the deprotonated acid.

If EDTA helps, it is because it is a 6 proton acid and will send off a few protons to lower the pH of the solution, negating the need for the salt.

thanks for the vinegar idea. i wonder if there is any way I could use vitamin C as my acid.

Vitamin C is too unstable.

 

[CCS]

Thanks for the info. I'm going to use organic apple vinegar. It will smell, but I don't care. Maybe the fatty acids I use in the cream will work too.

 

[Bryan]

Bryan (or anyone using spironolactone tablets),

Does home made spironolactone stink if you are not using minoxidil?

I've never noticed a smell from my own spironolactone concoctions, but I may have some genetic inability to notice it very strongly. I once had my two sisters try it out, too, by putting some of it on the backs of their hands (as they would if they were testing an expensive perfume! :lol: ), and they sniffed around it for quite a while. They said they didn't find it to be particularly objectionable.

One nice thing about Spirotone tablets is that they come with a very pleasant "minty" aroma. I'm sure it helps to mask the odor of the spironolactone.

Also, does PPG dissolve a lot of the tablet, or mostly just the spironolactone?

I have no earthly idea. I haven't tried any PPG-dissolving experiments with crushed spironolactone tablets.

Bryan, do you know if PPG can make a 4% spironolactone solution?

I have no idea about that, either. There's no information about it in the Merck Index.

It seems to me that we might get some solid answers to a lot of these spironolactone solubility questions by going straight to the companies that make it (preferably the one that first developed it). If my pal "maneless" was actually able to get through on the telephone to Dr. Hideo Uno and even Dr. Battmann (of RU58841 fame!), I'm sure we could call some company and ask to talk to some technical type who could answer questions like that for us...

I'd prefer spironolactone because if castration won't regrow hair, then I'd rather spend that money on Dr Proctor's SODs.

I think you've got the right idea. The purpose of all that reading and studying I did on things like castration, RU58841, spironolactone, flutamide, dutasteride, etc., was to try to nudge all the guys on the hairloss sites away from that simplistic idea that all you had to do to get your hair back was to find some kind of antiandrogenic treament that was sufficiently powerful. That was a constant theme on alt.baldspot, until I appeared on the scene! I wanted people to get used to the idea that there are limitations to what antiandrogens can do for hairloss, just like what Dr. Proctor has always said.

Bryan

 

[Bryan]

It'd be easier to use a coffee filter to separate the spironolactone solution from the gunk.

Yep. A coffee filter ought to work great.

Do you think spironolactone would be that hard to dissolve? I wonder what the Merck Index has to say about Spironolactone.

If I recall correctly, it just gives some typical information like "Spironolactone is soluble in [this, that, and the other]", but it doesn't give any specific numbers for solubility in those solvents.

Bryan