Capping and Preserving Accutane Raws

[BroScientist]

I have read up since ordering my accutane raws, and realized it's a bit more complicated than accutane + filler. Accutane apparently degrades quickly and is sensitive to light and moisture. My raws are now is a sealed jar with dessicant and the jar is in two cardboard boxes to keep light out. Next time I open the jar I'm going to nitrogen or argon purge the jar to keep out oxygen.

It seems that accutane is only oil soluble and being in oil seems to offer some protection from oxidation and other degradation. Since I'm going to go low dose (10-20mg/day) and only as long as I need, I'd like to both have a methodology for storage and for capping.

For long-term storage, I'm considering staying with the ziplock bag and dessicant in a nitrogen purged jar, in two boxes, with the boxes possibly painted black for light absorption. No tape on boxes, but the boxes seal well on their own.

For capping, I'm considering getting some plain coconut oil (hardish at room temperature), melting the oil (very little heat), combining with accutane, and metering into plain gelatin capsules with a syringe without needle. I may be able to immediately cap, or I may have to briefly put them into the freezer to harden before putting the top caps on. Caps should be stored somewhere cool in a dark jar.

Does anyone have a comment, especially @janoshik ?

 

[janoshik]

I have read up since ordering my accutane raws, and realized it's a bit more complicated than accutane + filler. Accutane apparently degrades quickly and is sensitive to light and moisture. My raws are now is a sealed jar with dessicant and the jar is in two cardboard boxes to keep light out. Next time I open the jar I'm going to nitrogen or argon purge the jar to keep out oxygen.

It seems that accutane is only oil soluble and being in oil seems to offer some protection from oxidation and other degradation. Since I'm going to go low dose (10-20mg/day) and only as long as I need, I'd like to both have a methodology for storage and for capping.

For long-term storage, I'm considering staying with the ziplock bag and dessicant in a nitrogen purged jar, in two boxes, with the boxes possibly painted black for light absorption. No tape on boxes, but the boxes seal well on their own.

For capping, I'm considering getting some plain coconut oil (hardish at room temperature), melting the oil (very little heat), combining with accutane, and metering into plain gelatin capsules with a syringe without needle. I may be able to immediately cap, or I may have to briefly put them into the freezer to harden before putting the top caps on. Caps should be stored somewhere cool in a dark jar.

Does anyone have a comment, especially @janoshik ?

You've summed it pretty well, except I ain't sure it will hold well in solidified coconut oil - only one way to find out and that's experiment.

Simpler approach would be to just dissolve it in 100 ml oil and dosing 1 ml with syringe. Have you considered that?

 

[Villain]

You've summed it pretty well, except I ain't sure it will hold well in solidified coconut oil - only one way to find out and that's experiment.

Simpler approach would be to just dissolve it in 100 ml oil and dosing 1 ml with syringe. Have you considered that?

Doesn’t mixing the raw with a filler and capping immediately help preserve it?

 

[janoshik]

Doesn’t mixing the raw with a filler and capping immediately help preserve it?

As compared to dissolving in oil and keeping it that way? Just dissolving in oil would be faster and therefore lead to less exposure, but that's just the first thought that occurs to me.

 

[BroScientist]

You've summed it pretty well, except I ain't sure it will hold well in solidified coconut oil - only one way to find out and that's experiment.

Yes. I'm also not certain that the oil won't dissolve the gel caps. That's going to be the first experiment.

Simpler approach would be to just dissolve it in 100 ml oil and dosing 1 ml with syringe. Have you considered that?

Maybe I'm just a pussy, but the reports of swallowing accutane that tastes like burning motor oil just doesn't sound really fun.
If the accutane does hold in oil, do you think it might be better to store accutane + coconut oil in a nitrogen purged jar, double boxed? Downside is that the bottle would have to be heated slightly to take some out.

Doesn’t mixing the raw with a filler and capping immediately help preserve it?

It depends. To get absorbed, accutane needs fats. The dosing instructions also say to take with a high calorie, fatty meal (1000 cals, +50% fat) which is going to be tough with making my macros. So starting with a non-fat filler, isn't great.

Or maybe I'm just being OCD about the whole thing. Wouldn't be the first time.

 

[janoshik]

Maybe I'm just a pussy, but the reports of swallowing accutane that tastes like burning motor oil just doesn't sound really fun.
If the accutane does hold in oil, do you think it might be better to store accutane + coconut oil in a nitrogen purged jar, double boxed? Downside is that the bottle would have to be heated slightly to take some out.

Never tried raw Accutane, but I did try raw DNP.
Both things are yellow and both are described as burning motor oil taste I guess you can say those are equal . Definitely not fun, but definitely doable.

I personally wouldn't bother with nitrogen and double boxing, I'd just keep it at freezer.

 

[Night_Owl]

Accutane only has a 20% absorption rate as an api if I recall correctly.

I don't know if the finished product has that accounted for.

And I'm not sure it's as simple as capping them in oil.

I'll try to do some digging. Cool project man, I always appreciate your posts.

 

[Night_Owl]

Ok found some things that might interest you:

Particle size and bioavailability.

Accutane ® contains isotretinoin with an average particle size of approximately 100 microns, resulting in only 20% oral bioavailability. Thus, this application discloses a composition of isotretinoin with particles of a smaller size, and, therefore, improved bioavailability when administered orally.

Suspension in capsules

Patents US 7,435,427 and 8,367,102 cover on the market Absorica ® composition. These patents disclose capsules containing a semi-solid suspension of isotretinoin containing at least two lipid excipients, one of which has a hydrophilic-lipophilic balance (HLB) value equal to or greater than 10, and the other is an oil carrier.

RU2707753C2 - Low-dose pharmaceutical composition of isotretinoin for oral administration - Google Patents

The present invention relates to an oral pharmaceutical composition of isotretinoin containing at least two excipients, one of them being hydrophilic (i.e.having an HLB value superior or equal to 10), and the other being an oily vehicle.

Very few publications and/or patents about the pharmaceutical formulation of isotretinoin are available. The drug is available on most markets under the form of a soft gelatin capsule containing a fatty liquid formulation of isotretinoin.

CA2836228A1 - Pharmaceutical semi-solid composition of isotretinoin - Google Patents

You might want to add some Taurine:

While taurine can be separately administered, it is preferred to administer both the retinoic acid derivative and the protective agent in a unitary dosage form to insure that the protection of human cells against damage from the retinoid is obtained.

The pharmaceutical composition of claim 1 wherein said composition comprises from 10 to 40 mg per unit dose of isotretinoin and from 10 to 4000 per unit dose of taurine.

US4545977A - Compositions and methods for treating severe acne with isotretinoin - Google Patents

And then the main one:

EP0184942B1 - Improved pharmaceutical composition containing 13-cis vitamin a acid as the active ingredient - Google Patents

 

[BroScientist]

@iamnightowl Interesting studies. I'll definitely add taurine, probably not to the same cap, but I can take them together. Usually I read all the literature, but I have been staying away on this one, I'm certain the side effects would scare me away. I'm hoping a low dose will mitigate some of that.

Never tried raw Accutane, but I did try raw DNP.
Both things are yellow and both are described as burning motor oil taste I guess you can say those are equal . Definitely not fun, but definitely doable.

I personally wouldn't bother with nitrogen and double boxing, I'd just keep it at freezer.

I'd assume DNP tastes pretty bad by it's distinct chemical smell. Since that stuff hits my stomach hard, it probably wouldn't help having my throat burn. Why didn't you cap it? Capping is easy.

I saw something that said not to freeze it. But if you don't put it in something sealed well with desiccant I can see the freezer being a problem with moisture.

 

[janoshik]

@iamnightowl Interesting studies. I'll definitely add taurine, probably not to the same cap, but I can take them together. Usually I read all the literature, but I have been staying away on this one, I'm certain the side effects would scare me away. I'm hoping a low dose will mitigate some of that.


I'd assume DNP tastes pretty bad by it's distinct chemical smell. Since that stuff hits my stomach hard, it probably wouldn't help having my throat burn. Why didn't you cap it? Capping is easy.

I saw something that said not to freeze it. But if you don't put it in something sealed well with desiccant I can see the freezer being a problem with moisture.

I synthetized DNP for fun and I generally don't keep empty caps in the lab. I was also quite impatient in my younger years

You definitely can freeze isotretinoin. Standards are delivered on dry ice. Must've been because of moisture or something.

 

[ickyrica]

Doesn't the toxicity increase as the potency decreases? Which would make long term storage of it a less than stellar idea, no?

 

[janoshik]

Doesn't the toxicity increase as the potency decreases? Which would make long term storage of it a less than stellar idea, no?

It does increase as it isomerises, which it does on exposure to light.

 

[Night_Owl]

Doesn't the toxicity increase as the potency decreases? Which would make long term storage of it a less than stellar idea, no?

Correct.

 

[Bulldog413]

I didn't know it was this critical. im storing my isotretinoin raws in a fireproof lockbox safe in a ziplock bag. Currently using HUMCO suspension in dropper bottles to make Accutane suspension. Used 49ml HUMCO with 1g Iso for 50ml @20mg/ml. Mabye I should get some 190 Everclear and make the remaining 19g I have up @ 40mg/ml in HUMCO and Everclear to preserve. would this work?

 

[BroScientist]

I didn't know it was this critical. im storing my isotretinoin raws in a fireproof lockbox safe in a ziplock bag.

Well, it's not good, but it's not quite as bad as the studies say either.
UVA is the major contributor to the photodegradation of tretinoin and isotretinoin: implications for development of improved pharmaceutical formulations
Even for the "visible light" study, they used 5 8-watt flourescent tubes at a distance of 36.5cm from the sample. That's a LOT of light, and they spread the sample very thin. Still, the accutane degrades quickly.

My own sample sat for some time on a shelf, in a ziplock in a jar with dessicant, behind a box in a room not well lit with florescent light. The sample wasn't spread thin though. I may get out my light meter to check for fun.

It might not be as bad as the graphs show, IIRC, 13RA partly decomposes to RA, but RA is metabolized into 13RA in the body. I need to read further, but it seems that when RA decomposes under light, that creates the toxic compounds. I'd have to research further, what exactly the "toxic" compounds are, and if they are any more "toxic" than 13RA in the first place.

An unrelated study comes to mind wherein the author somewhat chuckles and says that any impurities made in the production of DNP are actually less harmful than the DNP itself. We may have a similar case here. But I don't know, this is just conjecture.

I also don't know what other conditions are required for the light reaction, oxygen or moisture may additionally be required. In the study they don't specify what the ethanol preparation was, but it's very hard to get 100% ethanol, it's very hygroscopic and will pull moisture out of the air quickly. The cream formulation did have a water component.

Update on the oil and capsule experiment. About 0.1ml of soybean oil was put into a 00 capsule and the top was put in place. I left it out in a glass for 12 hours. The capsule didn't dissolve, and surprisingly, the capsule didn't leak. The oil filled the gap between the halves and stopped there.

Next steps:
1) Research "toxic" byproducts of isomerization.
2) Research if there is an easy way to purify degraded 13RA
3) Test solubility of 13RA in coconut oil.

I will mix up a batch of 13RA and coconut oil tonight and cap them if the 13RA goes into solution / suspension.

 

[Night_Owl]

@BroScientist any updates?

 

[BroScientist]

What a clusterfuck.

But first a update on the soybean oil in a OO capsule. After 24 hours, it ended up leaking, I think it was due to pressure changes, the temperature cooled down a bit, heated up, and pushed some of the oil out.

Back to the main event. I worked under a red light for the portions when I needed to have the 13RA out. Even with only the red light on and pointed at a wall, I kept the raws in shadow when I could. It was harder than I thought working in low light.

I heated the oil by placing my cylinder into boiling hot water, but only enough to fully melt the oil. The 13RA did not sufficiently dissolve into solution at a rate of 20mg/ml. I did transfer the solution to a bottle and shook it 100 times. Perhaps with a hot plate and a magnetic stirrer, the results might be different. The melt point of 13RA is really high, 374F, I'm not sure the oil could take that, but heating more than it was it would have probably helped to dissolve the 13RA.

I used a 23ga 5ml syringe to dispense and quickly found out that the needle would not work. So the needle was removed and work continued. I attempted to meter out 0.5ml per capsule (24 total), but ran out of solution at 20 caps. I think the 5ml syringe was too large for accurate metering in the 0.5ml range. Surprisingly, I didn't slop much in the low light, nearly all the solution went in the caps, there was little spillage. There was visible residue in my beaker and shake bottle. The final dosage of my caps is unknown, but assumed to be around 10ml/cap since I came up 4 short, but there was considerable residue and fall-out in the labware.

I immediately put the top caps on, put the capsules in a jar, wrapped the jar in tin foil and put it in the freezer. Inspection after an hour showed a fair amount of the 13ra accumulated in the bottom of the caps.

For science, I took one of the caps with 3000mg fish oil and some chocolate and went to bed. Sleep was terrible, accutane insomia is real. In the morning, my skin was bone dry, I didn't expect results so quickly. I'd definitely advise against nighttime dosing.

If I can't find out a way to get better absorption into the oil, capping with dry filler, or mixing with a different oil (and dosing with a syringe) may be better.

What oils has anyone used to dose their accutane and at what mg/ml?

 

[BroScientist]

I went and bought chapstick and hungrily opened it in the parking lot like a junkie that finally got his next hit.

I can't imagine taking 60mg of this shit daily, for months.

 

[BroScientist]

I think I'm going to be on 10mg 2x a week, and that should cover me. I need to buy a big ass hat, I was outside for maybe an hour on a very overcast day, still got very red. I doubt that 10mg 2x a week will set me up for a lifetime cure, but if it gets me clear, I could be ok with running it a while.
If you see a really white guy rocking a sombrero, give a wave, it's me.

 

[janoshik]

If you see a really white guy rocking a sombrero, give a wave, it's me.

Hey, me too mate. Sombreros are awesome.