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Making pure paracetamol by mixing with ethanol

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Ken Nadvornick

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I'm trying to make a clear Parodinal using paracetamol tablets, and mixing it with ethanol to separate the binders. Does the paracetamol crystals from this method keep well? Or should I make only small batch.

I am currently in the process of separating some paracetamol from tablet binders as well. I've made clear batches of Parodinal before, but never after having stored the extracted paracetamol crystals for more than a few days.

My assumption has always been that the binders, being inert, have no effect on storage and the tablets themselves keep quite well when stored normally in their factory containers. However, I don't know what preservatives, if any, may also be included in the mix. And whether those preservatives, if they exist, are non-soluble in alcohol.

Also, you may wish to know that the solubility of paracetamol in methanol is significantly greater than in ethanol. See tables 1 & 2 on page 1392 (PDF page 3) at the following link for a list of paracetamol solubilities in various solvents over a temperature range of -5C through 30C.

Solubility of Paracetamol in Pure Solvents
Journal of Chemical Engineering Data, Vol. 44, No. 6, pp. 1391-1395, 1999
Roger A. Granberg and Ake C. Rasmuson
Department of Chemical Engineering and Technology
Royal Institute of Technology, Stockholm, Sweden​

Ken
 
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daveandiputra

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Hi Ken,
Thanks for the links, i'll be sure to use methanol for my next try. Yes the tablets themselves keep for a long time based on the expiry dates on the sleeves. My scale broke and haven't got the chance to buy a new one, thats why I can't make the parodinal right now.
. My test (about two weeks ago), that I keep in a sealed clear plastic bag still have the same form and color. It is slightly pinkish in color.
Although I can just mixed a new batch later, I guess I just want to know the possibility making some on a larger amount and storing them.
Dave.
 

Ken Nadvornick

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My scale broke and haven't got the chance to buy a new one, thats why I can't make the parodinal right now.

My current approach takes advantage of the fact that paracetamol (acetaminophen) in tablet form is already premeasured, most tablets being 500 mg. While I don't know the precision of that measurement, for the purposes of a DIY film developer I've simply assumed that, given it's for human drug consumption, it's probably close enough.

Here's what I am trying in my latest batch:

(1) Measure 400 ml of methyl alcohol (methanol) into a sealable container. I've been using glass wide-mouth Kerr canning jars with a quadruple fold of Saran food wrap as a gasket. 400 ml is approximately four times the minimum requirement at 20C/68F, but is a minimum for my workaround procedure.

(2) Add 80 500 mg tablets to the methanol and seal the jar. No crushing is required. Just drop them in, then shake the jar every few minutes. In about two hours the paracetamol will have separated completely from the binder. This puts about 40 grams into the 400 ml solution.

(3) Set the mixture aside for about 3-4 days. Leave it completely untouched so that gravity can do its work. The solids will completely settle out leaving a near crystal clear liquid. If you want true crystal clear, wait about a week. This is my workaround for not owning a vaccum filter flask or centrifuge. If I was going to do this on a regular basis, I'd invest in a flask and hand-pump or aspirator.

(4) Since the Parodinal formula calls for 30 mg of paracetamol for 500 ml of developer, I next use a 60 ml syringe (intended for livestock, not humans, so it's easy to source) to carefully remove 300 ml of clear solution from the jar. This is why I need 400 ml to start. The residual solids fit comfortably into that remaining 100 ml at the bottom and don't contaminate the 300 ml I've removed. 300 ml contains 30 mg of paracetamol. No scale is thus required.

(5) Place the removed 300 ml of solution into a 500 ml beaker and allow the methanol to completely evaporate. I help this process along by immersing the beaker into a waterbath held at exactly 52C/125F by a one of those Corning hot plate stirrers equipped with a feedback thermometer. I chose 52C/125F because the boiling point of methanol is 65C/149F and I don't know enough chemistry to anticipate whether boiling the methanol away more quickly will alter the crystallizing paracetamol at that temperature. Make certain there is sufficient ventilation in place to remove the methanol fumes. If not, perform this step outside. I've never tried using the sun on a warm day, but it might work.

(6) When the methanol is gone, add 400 ml of distilled water at 7C/45F into the beaker containing the crystallized paracetamol. Place the beaker into an ice bath for safety. Place a thermometer into the beaker.

(7) Using eye protection, gloves, and protective clothing, slowly add 40 grams of anhydrous sodium hydroxide into the beaker. Watch the temperature on the thermometer. Go slowly enough that any excess heat bleeds out into the ice water, but leave enough heat to help dissolve the sodium sulfite in the next step. I aim for the usual 52C/125F. The solution should turn a slight pinkish, but still be transparently clear.

(8) Once the paracetamol is completely dissolved, adjust the temperature to 52C/125F and add 50 grams of sodum sulfite. This is only half the amount called for in the original Parodinal formula. My experience has been that 100 grams sulfite per 500 ml of solution is beyond saturation at room temperature. I always seemed to have a significant excess that would not dissolve. So I'm trying the more standard developer concentraton of 100 grams per liter to see how that works out.

(9) Once the sodium sulfite is completely dissolved, add cold distilled water to bring the total volume up to 500 ml. Store as you would any other film developer.

I'm trying several new things with this, so if the above steps end up producing a failure - or disaster - I'll ask the moderators to remove this post.

Ken
 

BirgerA

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.

(2) Add 80 500 mg tablets to the methanol and seal the jar. No crushing is required. Just drop them in, then shake the jar every few minutes. In about two hours the paracetamol will have separated completely from the binder. This puts about 40 grams into the 400 ml solution.

(3) Set the mixture aside for about 3-4 days. Leave it completely untouched so that gravity can do its work. The solids will completely settle out leaving a near crystal clear liquid. If you want true crystal clear, wait about a week. This is my workaround for not owning a vaccum filter flask or centrifuge. If I was going to do this on a regular basis, I'd invest in a flask and hand-pump or aspirator.

(4) Since the Parodinal formula calls for 30 mg of paracetamol for 500 ml of developer, I next use a 60 ml syringe (intended for livestock, not humans, so it's easy to source) to carefully remove 300 ml of clear solution from the jar. This is why I need 400 ml to start. The residual solids fit comfortably into that remaining 100 ml at the bottom and don't contaminate the 300 ml I've removed. 300 ml contains 30 mg of paracetamol. No scale is thus required.

It has been a while since I used my chemistry degree, but I wonder if you have a mistake here between step 2 and 4 (or you may know something that I don't). If you have 40 grams of paracetamol in your solution in step 2, and 30 milligrams of paracetamol in 75% of your solution in step 4, where did 39.970 grams of paracetamol go?
 
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Gerald C Koch

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Tylenol and generics contain N-acetyl paraminophenol and fillers to allow the ingredients to be made into pills. According to the US Pharmacopoeia, "fillers are chemically inert, compatible with other ingredients, water soluble, relatively cheap, colorless and tasteless." The fillers can be removed at any time before the use of the developer. Since the fillers are insoluble the easiest method is to prepare the developer and then filter the resulting solution. Since the amount of the active ingredient is stated on the label, the pills do not need to be weighed.

The N substituted aminophenols are far less sensitive to oxidation than the parent chemical paraminophenol. This is why Metol and Glycin are used as developers. First isolating the acetyl paraminophenol by dissolving it in alcohol represents an unnecessary step.
 

Ken Nadvornick

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It has been a while since I used my chemistry degree, but I wonder if you have a mistake here between step 2 and 4 (or you may know something that I don't). If you have 40 grams of paracetamol in your solution in step 2, and 30 milligrams of paracetamol in 75% of your solution in step 4, where did 39.970 grams of paracetamol go?

Oops. Yes, a typo as Alan also points out below. It obviously should be 30 grams, not 30 milligrams. I did try to proof read before posting, but chose the absolute worst person in the world to do it...

:wink:

In para (4) where it twice says 30mg Paracetamol it is a typo, it should be 30g Paracetamol for 500ml developer.
http://www.digitaltruth.com/data/parodinal.php
I make clear Parodinal from the type of capsules whose contents can be tipped out and weighed.I also use half the amount of sodium sulfite given in the above formula.

So Alan, with only half the sulfite in solution (100 versus 200 grams/liter) do you notice any adverse performance or keeping properties with your mix?

The N substituted aminophenols are far less sensitive to oxidation than the parent chemical paraminophenol. This is why Metol and Glycin are used as developers. First isolating the acetyl paraminophenol by dissolving it in alcohol represents an unnecessary step.

As I said, my background is not chemistry, so please bear with me. In previous batches I have tried - where I did not first isolate the paracetamol - the solution ended up (after settling) with a significant amount of frothing floating on the surface in addition to the filler solids (mixed with excess sulfite) on the bottom.

My working guess is that the frothing is somehow related to the fillers and not the sulfite, since no other sulfite-containing developers I mix show similar frothing. So I am trying to see what happens if I first remove the fillers and also cut the sulfite in half. (I know, two variables at once, but this is just for fun.) And since the solvent being used is alcohol and not water, I'm guessing that in a near-full, sealed container oxidation will not be a significant problem. Does this make sense?

And to the OP's original question, what would be your opinion regarding the keeping properties of paracetamol that has been separated from the tablet binders, even if that isolation step may not be absolutely necessary?

Thanks Jerry,

Ken
 

Alan Johnson

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I have kept some PaRodinal relics, about 1/8 full bottle, to see how they age.
(1) 33 months old digitaltruth formula, cloudy with filler, many crystals, probably sulfite.
(2) 21 months old clear PaRodinal with half strength sulfite, a few crystals of unknown composition.
Negatives from (1) are losing density but still printable.
Negatives from (2) look OK but have not been compared with fresh PaRodinal.

Using only half sulfite did not have any detectable effect on the shelf life.
It is preferable though not to keep just a little in a near empty bottle.
 

Gerald C Koch

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And to the OP's original question, what would be your opinion regarding the keeping properties of paracetamol that has been separated from the tablet binders, even if that isolation step may not be absolutely necessary?

I would say that the keeping properties would be excellent.

As to the frothing, different brands may use different fillers. Some brands may not produce frothing.
 

Ken Nadvornick

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Thanks and Please share the result Ken :smile:

Yikes! Not exactly sure what I ended up with tonight. Won't even know if it's a developer for another 72 hours. But I gotta tell ya', it's absolutely gorgeous to look at in a clear bottle...

Steps 1-4 went exactly as planned.

In Step 5 I skipped the waterbath and precision temperature control and just set the beaker with a suspended thermometer on the hot plate and manually adjusted things to 50C/122F. I used a stir bar until evaporation reached 100ml of solution remaining. Then I removed the bar, turned the temperature down and let the final crystallization take place.

In Step 6 the water went in at 10C/50F.

Step 7 caused the crystalized paracetamol to mostly dissolve, but again there was residual frothing. Not nearly as bad as before without the binder separation, but still some present. Highest temperature reached was 27C/81F.

In Step 8 I neglected to adjust the temperature up to 52C/125F before adding the sodium sulfite. It took the 50g quite a while to completely dissolve. I turned up the hot plate until the solution reached 52C/125F to help things along. Eventually it all dissolved. At this point the solution was a light pinkish-tan color, transparent, but with froth floating on the top and more suspended within, giving it a cloudy look. There were no undissolved crystals of any kind on the bottom.

For Step 9 I decided to filter the solution into a graduate, then top it off to 500ml. I reached for my usual brown-colored coffee filters. Unfortunately, I don't think I've ever before used those to filter a solution containing 80g/liter of sodium hyroxide. So as my pinkish-tan color went in the top, an absolutely beautiful amber-brown color emerged from the bottom, thankfully minus any of the froth.

But damn. It looks for all the world like Jack Daniels Old No. 7 Brand Tennessee Sour Mash Whiskey...

:eek:

Leached the color right out of the filters, so at this point I have no idea if this new variable has ruined everything. And I'm certainly not going to be able to judge any subtle color changes with age. All I know is it was pinkish-tan to begin with.

Does anyone know what's in those natural brown coffee filters that give them their color? Just my luck it will probably be a huge restrainer. Guess I need to invest next time in some real filters.

Well, even if this stuff can't develop a single frame of exposed film, it will still be a damned impressive looking, crystal clear shelf queen. Only time will tell.

Ken
 
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daveandiputra

daveandiputra

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I would say that the keeping properties would be excellent.

As to the frothing, different brands may use different fillers. Some brands may not produce frothing.

thanks jerry, i will try to make a small batch from the test run I made before. But for that I'm going to need a new scale to measure the ingredients :smile:

Yikes! Not exactly sure what I ended up with tonight. Won't even know if it's a developer for another 72 hours. But I gotta tell ya', it's absolutely gorgeous to look at in a clear bottle...

Steps 1-4 went exactly as planned.

In Step 5 I skipped the waterbath and precision temperature control and just set the beaker with a suspended thermometer on the hot plate and manually adjusted things to 50C/122F. I used a stir bar until evaporation reached 100ml of solution remaining. Then I removed the bar, turned the temperature down and let the final crystallization take place.

In Step 6 the water went in at 10C/50F.

Step 7 caused the crystalized paracetamol to mostly dissolve, but again there was residual frothing. Not nearly as bad as before without the binder separation, but still some present. Highest temperature reached was 27C/81F.

In Step 8 I neglected to adjust the temperature up to 52C/125F before adding the sodium sulfite. It took the 50g quite a while to completely dissolve. I turned up the hot plate until the solution reached 52C/125F to help things along. Eventually it all dissolved. At this point the solution was a light pinkish-tan color, transparent, but with froth floating on the top and more suspended within, giving it a cloudy look. There were no undissolved crystals of any kind on the bottom.

For Step 9 I decided to filter the solution into a graduate, then top it off to 500ml. I reached for my usual brown-colored coffee filters. Unfortunately, I don't think I've ever before used those to filter a solution containing 80g/liter of sodium hyroxide. So as my pinkish-tan color went in the top, an absolutely beautiful amber-brown color emerged from the bottom, thankfully minus any of the froth.

But damn. It looks for all the world like Jack Daniels Old No. 7 Brand Tennessee Sour Mash Whiskey...

:eek:

Leached the color right out of the filters, so at this point I have no idea if this new variable has ruined everything. And I'm certainly not going to be able to judge any subtle color changes with age. All I know is it was pinkish-tan to begin with.

Does anyone know what's in those natural brown coffee filters that give them their color? Just my luck it will probably be a huge restrainer. Guess I need to invest next time in some real filters.

Well, even if this stuff can't develop a single frame of exposed film, it will still be a damned impressive looking, crystal clear shelf queen. Only time will tell.

Ken

Nice Ken, am sure waiting for the result
I won't have the access to hot plate stirrers, hopefully just plain old manual stirring and process will do, just as my first Parodinal try.
 

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The one and only time I made clear Parodinal, about 6 years ago, I evaporated the alcohol from the solution by pouring it in a wide shallow tray. Then I propped up an electric hair dryer a short distance from the tray and turned it on the low setting. I adjusted the hair dryer so the air was blowing on the tray of solution at a shallow angle and far enough away to not agitate the solution too much or splash any of it out of the tray. I could see little ripples in the surface of the solution as the warm air moved across it. About two hours later, all the alcohol was evaporated. I did this in the garage with the main door and side door open for ventilation, and made sure no other electrical appliances were running.
 
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daveandiputra

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The one and only time I made clear Parodinal, about 6 years ago, I evaporated the alcohol from the solution by pouring it in a wide shallow tray. Then I propped up an electric hair dryer a short distance from the tray and turned it on the low setting. I adjusted the hair dryer so the air was blowing on the tray of solution at a shallow angle and far enough away to not agitate the solution too much or splash any of it out of the tray. I could see little ripples in the surface of the solution as the warm air moved across it. About two hours later, all the alcohol was evaporated. I did this in the garage with the main door and side door open for ventilation, and made sure no other electrical appliances were running.

Hi desertrat, my first try is actually inspired from reading your post on that thread :smile:
 

Murray Kelly

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Jerry, you have me confused. Not difficult I admit, but the USP as quoted says the fillers are among other things, water soluble. Then you go on to say they are insoluble. Which is it?
Murray

Tylenol and generics contain N-acetyl paraminophenol and fillers to allow the ingredients to be made into pills. According to the US Pharmacopoeia, "fillers are chemically inert, compatible with other ingredients, water soluble, relatively cheap, colorless and tasteless." The fillers can be removed at any time before the use of the developer. Since the fillers are insoluble the easiest method is to prepare the developer and then filter the resulting solution. Since the amount of the active ingredient is stated on the label, the pills do not need to be weighed.
 

Gerald C Koch

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Jerry, you have me confused. Not difficult I admit, but the USP as quoted says the fillers are among other things, water soluble. Then you go on to say they are insoluble. Which is it?
Murray

I didn't catch that, so am I. :sad: I was pointing out that they were inert and would not effect the keeping properties of the developer. Certainly the two most common fillers cellulose and starch are not soluble in water. Sometimes the word soluble is used when the more exact term disperse should be used. Cookbooks will commonly say "dissolve the starch in a small amount of water."
 

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Hi desertrat, my first try is actually inspired from reading your post on that thread :smile:
Thanks! I guess it's kind of obvious now your forum searching skills are a lot better than my memory...:redface:
 

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I'm trying to make a clear Parodinal using paracetamol tablets, and mixing it with ethanol to separate the binders. Does the paracetamol crystals from this method keep well? Or should I make only small batch.

No it doesn't keep well, you need to separate it and then get it into solution with preservative (ie: get onto making the parodinal with it).
 

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Athiril

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On what do you base your assertion? As I stated earlier the N substituted paraminophenols are more stable than the parent paraminophenol. The following site http://www.pharmweb.net/pwmirror/pwy/paracetamol/pharmwebpicm.html says that a saturated water solution has a half-life of twenty years.

The op asked;
"Does the paracetamol crystals from this method keep well?"

He didn't ask about a stock solution, and which of course a saturated water solution of paracetamol is completely useless due to how much you can actually dissolve in water at room temperature doesn't match up to what you need to make a PaRodinal formulation. Other solvents are out of the question as most people will be using sodium salts not potassium salts (the sulphite) - you need all the solvent to be water when using sodium salt formula of PaRodinal, otherwise you can't dissolve everything properly.

At the very least to make a PaRodinal formulation you need to get rid of the alcohol and reduce the volume of solvent to the required amount - you can add water and keep evaporating the alcohol off.

And I am basing the instability of the extracted dry form on first hand data. Once you extract the compound from the solution, dry and and grind it, it will oxidise and turn burn even in jars quickly. It doesn't last very long.


Hi Ken,
Thanks for the links, i'll be sure to use methanol for my next try. Yes the tablets themselves keep for a long time based on the expiry dates on the sleeves. My scale broke and haven't got the chance to buy a new one, thats why I can't make the parodinal right now.
. My test (about two weeks ago), that I keep in a sealed clear plastic bag still have the same form and color. It is slightly pinkish in color.
Although I can just mixed a new batch later, I guess I just want to know the possibility making some on a larger amount and storing them.
Dave.


Methylated Spirits is inexpensive and works fine for this purpose.


You can always weigh 10 or 100mL etc etc of your solvent with the paracetamol in it to find out how much is actually in there.
 
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Gerald C Koch

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And I am basing the instability of the extracted dry form on first hand data. Once you extract the compound from the solution, dry and and grind it, it will oxidise and turn burn even in jars quickly.


Very curious. The tablets appear stable but once extracted the acetaminophen turns brown. I have some tablets that are at least 5 years old and show no discoloration. I will have to try this out.

I quoted the stability of the water solution since such solutions are more susceptable to oxidation than the solid would be.
 
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