Rapamycin enteric coating vs powder bioavailability

Dr. K answered by question by email. Sounds like the powder form might be greatly inferior:

"I thought we addressed this in the AMA, but here are my thoughts on the enteric coating.

The generic tablets (Rapamune, sirolimus) that have the characteristic triangle shape should have comparable bioavailability and are formulated for good uptake. The reason the mouse ITP used a special enteric nano-formulation (eRAPA) is because the raw powder is unstable at gastric pH. I have heard of at least one case where compounded rapamycin in a capsule had very poor bioavailability compared to the tablets, likely due to this reason. Hope that helps.

Matt"

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This is probably very true. I just increase my dose, my powder is so cheap. I am looking into enteric coated delivery, but yet another variable.

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Most all of India’s API’ all come from China…I didn’t know that.

But if you’re just absorbing a fraction of the powder/capsule dose (and who even knows what fraction?), and that’s assuming the chinese powder is actually 100% rapamycin in the first place, it completely totally throws off any kind of dosage guesstimation.

I’ve been buying rapa capsules from a vet for my dogs, but clearly I need to find a way to get them the tablets now, too, since dogs’ stomach environment is even more acidic than humans.

Blood Sirolimus will be my guide. I already confirmed it’s Sirolimus, other thread. Many others before me are using same vendor, but I take nothing for granted, I will need blood tests to verify.

I am planning on doing a blood Sirolimus panel shortly. Will measure time zero trough (I am doing weekly no GFJ currently), and then do 4 or 5 tests post dose, 30min, 60 min, 90 min, 120 min, 150 min post dose to see if I can capture approx Cmax.

The enteric will bypass the stomach and empty into the lower intestine. This is another variable I’ve parked to the side.

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BTW if stomach acid is the culprit, it should be possible to significantly increase absorption of a once weekly dose of rapamycin by pre-medicating with a stomach acid reducing med such as famotidine, where one dose in the evening followed by a second dose in the morning increased gastric pH from 1.3 to 6.6 (!!!)

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That is very interesting indeed.

But that’s yet another variable and med with what level of controllable efficacy? And I cannot even imagine the disruption in the gut microbiome messing with homeostasis pH?

If not using Pharma grade tablets, I think it would be far simpler to just bypass the stomach, and use good quality enteric capsule with known delay in emptying until reaching lower intestine?

Maybe, if the enteric capsules actually work as advertised. Would a once weekly dose of famotidine (with a quick elimination half-life of only 3 hours) cause any kind of disruption of intestinal flora?

In any case, yes I agree it seems more straightforward to try the enteric caps first to see if they work before introducing yet another medication variable. From what I’m reading, it seems important to take the enteric caps on an empty stomach since food might increase gastric pH enough to cause the caps to open in the stomach.

I think these enteric capsules have been around for a long time, I think they work. Certainly would want to do a careful vendor selection and rigorous enteric capsule/Rapamycin experiment. Like I said, after my next Rapamycin powder experiment, I will revisit enteric coated capsules. I shudder at messing with my stomach pH.

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Yes - but its a concentrated industry like most industries, so for any given API (Active Pharmaceutical ingredient) - most of the supplies probably come from 4 or 5 vendors. And - for each API - the different final product manufacturer in India will have different quality controls both on incoming APIs from china, and also in their own production processes… so still lots of variables go into the quality of the final product we buy.

And - as far as buying powder from china - anyone purchasing small amount of powder (e.g. under a kilo) - you’re most likely going through a middleman and they won’t tell you the actual manufacturer… so lots of blindspots with regard to quality for individually purchased powders… if the vendor says they are selling materials they produce themselves, I would find that even more scary because any vendor selling grams of sirolimus to an individual has to be an extremely small manufacturer - and generally in any market, the vendors that have under 1% of the market, are the very poorest in terms of quality control. They just can’t compete given the volumes they produce. Same with most manufacturing industries.

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A document titled “SIROLIMUS – sirolimus tablet, film coated”, “Zydus Pharmaceuticals (USA), Inc.” says “Each sirolimus tablet intended for oral administration contains 0.5 mg of sirolimus. In addition, each tablet contains the following inactive ingredients: citric acid monohydrate, crospovidone, FD&C yellow #5 aluminum lake, glycerol monostearate, iron oxide yellow, lactose monohydrate, microcrystalline cellulose, poloxamer, polyethylene glycol, povidone, sucrose, talc, titanium dioxide and vitamin E acetate.”

I am not keen on ingesting certain of those ingredients. I found a compounding pharmacy that will create capsules containing only rapamycin powder and cellulose, in either regular quick-dissolving gelatin capsules or vegetarian time-release capsules. This pharmacy does not have enterically coated capsules as an option. I am not keen on altering my stomach acid, and I am concerned about the bioavailability issue I learned about in this thread. The vegetarian time-release capsule would likely have better bioavailability than a quick-dissolving gelatin capsule, but I wonder if anyone here knows of a better way to avoid the unpronounceable ingredients in regular rapamycin tablets while also preserving bioavailability. E.g., is there a compounding pharmacy that will leave out most inactive ingredients and put just rapamycin and cellulose in an enterically-coated capsule? My doctor is on board with prescribing rapamycin for me.

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I experimented with these “time released” capsules promoted on Amazon to see if we could perhaps bypass the stomach and minimize 1st pass effect. But they are USELESS. The dissolution curve clearly shows penetration of the contents immediately, something I verified with at home testing.

Perhaps your pharmacist can find you truly pharma grade enteric coated capsules that can bypass stomach (you need to look at the documented dissolution data) if you are highly motivated in this pursuit. Of course, you could just take more, but more $.

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What about:

I highly doubt anything sold on amazon is engineered for unencumbered contents passage through ph 1.5 stomach.

Ask vendor for dissolution data.

Their claim is slick and misleading:

“Our acid-resistant capsules are engineered to break down in the small intestine, instead of the stomach”

Sure, the caps themselves might not break down, but the prized contents have well spilled already in the stomach.

Look elsewhere.

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The capsule you should look at is the brand named “Acid Armor™”

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Glad to learn this before wasting money. Thanks to all for taking the time to reply. I’ll look into the “Acid Armor™” product and/or see if another compounding pharmacy will do something different.

Do we actually know or have data that Acid Armor works any better?

As a new forum member this may not be the best way to introduce myself, but has anyone considered using rectal suppositories to try to circumvent this issue with stomach acid? Perhaps this is a particularly poor idea, but I’d love to hear if that is the case and why this should be avoided. Admittedly I’m considering trying this out, as I also have powdered Rapamycin. It seems to have dissolved well in an alcohol solution, and I added it to a normal vegan capsule. But I don’t seem to get similar effects to the Rapa I bought previously from an Indian based pharmacy - even while taking much higher doses.

The website of the manufacturer of Acid Armor™ says “Acid Armor capsules have been shown in studies to delay the release of the capsule’s contents by an average of 45 minutes. When a product like Neprinol is taken on an empty stomach, the capsule typically enters and leaves the stomach in 30 minutes or less.” More info at the site:

I’m planning to put other capsules inside Acid Armor capsules, if they will fit, and see what happens. I may get my blood tested for the level of rapamycin a few hours after ingesting, or just see what happens to my regular blood parameters and symptoms of aging after I’ve been taking rapamycin for a while.

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Do we know for sure if an Acid Armor capsule will open up like a typical gelcap, or is it sealed? If it’s sealed, then we’re SOL when it comes to replacing the contents with rapamycin.