Levothyroxine tablet formulation challenge - Thyroid UK

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Levothyroxine tablet formulation challenge

helvella
helvellaAdministrator
130 Replies

Whenever a particular levothyroxine tablet is mentioned, at least someone reports that they cannot tolerate it. Quite often a lot of people.

Whether it is thought (or proved) to be the lactose, acacia, mannitol, dyes (not in any UK products), microcrystalline cellulose or any other excipient (inactive ingredient).

A typical tablet might weigh over 50 milligrams. Of which, perhaps 0.2% is active ingredient.

(As an example, one particular 100 microgram tablet contains 48.86 milligrams of lactose.)

As a challenge to all our readers, imagine a pharmaceutical company asked YOU to formulate a new tablet, what excipients would you choose? It is so easy to see the issues with the currently available tablets but another thing altogether to come up with an acceptable alternative.

Obviously almost none of us know anything about the realities of manufacturing levothyroxine tablets. This is pure fantasy and for fun and discussion - but it would be good to be as realistic as possible.

I have been mulling this over for years and still can't make my mind up what I would choose.

130 Replies
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RedApple
RedAppleAdministrator

Chocolate!

Ooops, just realised you want a serious answer :D

13 likes
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helvella
helvellaAdministrator
in reply to RedApple

Taking a po-faced serious view, for a moment, there is a problem with chocolate on hot summer days. Would you consider a sugar shell like M & Ms?

7 likes
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Sybilla14
Sybilla14
in reply to helvella

But only white!

1 like
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helvella
helvellaAdministrator
in reply to Sybilla14

That is a good point.

1 like
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Jnetti
Jnetti
in reply to Sybilla14

I hate white chocolate!

1 like
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helvella
helvellaAdministrator
in reply to Jnetti

That was white sugar coating to avoid colouring agents, not white chocolate! (At least, that is how I read it. :-) )

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Sybilla14

Dark chocolate! Think of the antioxidant boost too😉

8 likes
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RedApple
RedAppleAdministrator
in reply to Sybilla14

Me too (72% ish) :D

2 likes
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helvella
helvellaAdministrator
in reply to Sybilla14

One track mind. Huh! :-)

4 likes
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silverfox7
silverfox7
in reply to helvella

I found though some time ago but mentioned it fairly recently that I was craving chocolate and one other thing which I can’t remember now but I asked Google why and was told because it was high in magnesium then my body was asking for more and it was the same for the two I was craving so I upped my magnesium and the cravings stopped so high quality dark chocolate should be included as a serious suggestion! May be one with sea salt in it!

5 likes
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Jnetti
Jnetti
in reply to Sybilla14

Only problem is, if you make them too tasty we would be overdosing

4 likes
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Sybilla14
Sybilla14
in reply to Jnetti

Or optimising our doses😉

4 likes
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jgelliss

What I would love is to have Levo with the least fillers Corn Lactose Acai and dye free. Would also like the pill to be scored so that it can easily be split with our fingers but not to soft either .

There is room for improvements lets hope that they hear and listen to us . We are the ones that use it after all.

5 likes
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helvella
helvellaAdministrator
in reply to jgelliss

I agree with your aim - but what would you use instead?

1 like
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Nanaedake

What about mode of delivery? Is tablet the best given that so many people seem to have stomach problems?

3 likes
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helvella
helvellaAdministrator
in reply to Nanaedake

Seems unlikely to me that tablets are the best form. However, while they are the the only real option for most of us, I guess it is as well to come up with the best ideas for them! :-)

2 likes
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SilverAvocado

A patch might be nice. Are they slow release?

1 like
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linda96

If the levo was put as micro dots onto rice paper?

14 likes
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helvella
helvellaAdministrator
in reply to linda96

I know some medicines have been supplied like that. Has anyone ever heard of levothyroxine in that form? Seems a reasonable idea. :-)

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Nanaedake
Nanaedake
in reply to helvella

Rice paper dots sounds like a jolly good idea to me. In fact, how about rice excipient? Lactose suits me but not everyone.

3 likes
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helvella
helvellaAdministrator
in reply to Nanaedake

Rice starch (approved by FDA as an excipient):

usp.org/harmonization-stand...

Rice husk - research:

jmaterenvironsci.com/Docume...

1 like
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linda96
linda96
in reply to helvella

So not so unreasonable after all?

6 likes
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humanbean
humanbean
in reply to linda96

I love your idea!

2 likes
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Babette
Babette
in reply to linda96

That's a great idea but would need to be able to be split into smaller doses.

2 likes
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helvella
helvellaAdministrator
in reply to Babette

Remember the game Rock–paper–scissors?

Forget the rock. Just cut the paper with scissors. :-)

Impregnated paper seems to be quite widely used for illegal drugs.

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LunaMa

I’d like it in a flavoured spray, like the Better You vitamins, but Pimms rather than fruit flavoured 🍹

6 likes
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helvella
helvellaAdministrator
in reply to LunaMa

But what would you use to make the liquid that they need to put into a spray?

1 like
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LunaMa
LunaMa
in reply to helvella

Whatever it is they use in other sprays. Having said that I suppose the Pimms flavour might be hard to replicate, so if absolutely necessary I would be prepared to slum it with the real thing 🍹

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humanbean

I would like thyroid hormones to be put into olive oil which is put into gelatine (or gelatine-like) capsules. In other words, I would like them to be like some of the better quality vitamin D supplements.

I also really like the idea of the rice paper dots that linda96 has suggested.

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Poniesrfun

Tirosint comes in a gel cap. It lists T4, gelatin, water and glycerin as ingredients.

7 likes
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helvella
helvellaAdministrator
in reply to Poniesrfun

Glycerin (also called glycerol) has already been mentioned, recently, as the possible cause of issues with liquid levothyroxin.

Sadly.

2 likes
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Jnetti
Jnetti
in reply to helvella

Didn't know that

1 like
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Sybilla14
Sybilla14
in reply to helvella

Possibly because glycerine seems to always contain preservatives, which are not necessarily listed?

2 likes
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helvella
helvellaAdministrator
in reply to Sybilla14

Not impossible. But I suspect that a lot of the issues are due to micro-organisms which can use glycerin as a substrate.

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birkie

Hi

Does anyone know if you can get Levo in liquid form....🤔🤔

2 likes
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helvella
helvellaAdministrator
in reply to birkie

In the UK there are two or three makes of liquid levothyroxine. They use glycerol and various other ingredients. Some like but some find it upsets their guts.

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birkie
birkie
in reply to helvella

Hi helvella

Just asked because I have colitis I'm not getting on well with thyroxine my TSH is still suppressed my T3 is on the floor and my T4 is just 18% above I've been on Levo for over six months..my ferttin is low and my vit D...I'm having blood work done on the 6th of Nov...I'm not good at taking synthoid meds had server problems on anti thiyroid drugs which had me in hospital with thiyroid Storm because I kept vometing them back I fear the same thing might be happening with the Levo...my GP wasn't to take me off Levo for six weeks to see if my TSH rises....I've posted this problem on her got some great advise....but I'm thinking the Levo cud be upsetting my bowls 😩😩

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Myro
Myro
in reply to birkie

I would try NDT like armour. Because of small need and possibly good effects. It has T3 which seems you don't convert from T4 properly. But make you to be able to manage dose by symptoms. If medicine has lactose try without its. If colitis, irritable, nervous stomach it is not advisable to take lactose . Noone say if there is food which don't harm transfer- absorption of T4 into bloud and don't cause troubles. It is always sad to take on empty stomach. What about sugar wather? Ok sugar is poison. But a tea spoon a day is not tragedy. But it increases insuline and cause hunger. In 20 minutes - just in time for breakfast. Like eggs, chicken, fried vegetable no carbohidrates. A tea spoon is enought. Like an explosion.

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TSH110

Would avocado oil work? A few vitamins too! Nice with olive oil and rice dots!

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helvella
helvellaAdministrator
in reply to TSH110

Apparently avocado oil has a shelf-life of a year, unopened. I think you would need to add some substances to enhance shelf-life to at least two years.

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TSH110
TSH110
in reply to helvella

Cider vinegar?

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Jnetti
Jnetti
in reply to TSH110

Good idea. The acidity would help absorption. In a softgel? What would you use for outside?

1 like
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TSH110
TSH110
in reply to Jnetti

Almond paste for some extra magnesium 😎 hopefully it would make a nice thin crunchy encapsulation and taste nice till the cider vinegar and avocado oil hit!

3 likes
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Nanaedake
Nanaedake
in reply to TSH110

No good for nut allergies tho.

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TSH110
TSH110
in reply to Nanaedake

Good point - crushed pumpkin seeds maybe? They’re not nuts

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SilverAvocado

In terms of storing ACV I've heard it needs to be glass, and seen horror stories of plastic bottles being melted. So the coating would need to be pretty substantial!

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silverfox7

You can now take ACV in a more sweet type form called Gummies I think it’s called so no horrible taste and it tastes more like apples but it also includes things like beetroot and other things to mask any ACV taste so alternatives may not be an impossible dream!

1 like
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helvella
helvellaAdministrator
in reply to Jnetti

Levothyroxine is very insoluble in neutral and acid. It is a bit more soluble in alkalis.

Not sure vinegar would help. :-(

1 like
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Jnetti
Jnetti
in reply to helvella

Vitamin C is a weak acid too, and supposed to be good to help absorption

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helvella
helvellaAdministrator
in reply to Jnetti

True - but it might not just be the pH that results in slightly improved solubility (or absorption) of levothyroxine with ascorbic acid.

1 like
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Myro
Myro
in reply to TSH110

Oils don't absorb fast.

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helvella
helvellaAdministrator
in reply to Myro

Would that be an advantage or a disadvantage?

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Myro
Myro
in reply to helvella

If T4 stay in intestines in oil solution or fine particles of coffee ... Is lost. Farmacy generally prove absorption and recommend proven way. There is many things which can have effect. From stability of T4 to problem of mcg of medicine. I think that even saince doesn't research that field. You can try something which you thing is good. Observe symptoms. That means that you are common with symptoms of hipotiroditis hipertiroidis and lack of iodine and conseqvences. After certain time test of all thyroid hormones is needed. To prove you are doing good. Don't try more than one thing a time. In olive and some other oils have some oils which stay in intestines and are good for ...

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TSH110
TSH110
in reply to Myro

Could work as a slow release mechanism. 😉

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Myro
Myro
in reply to TSH110

It should be proven. But for T4 it is not so important. Amount of drug ( hormone) is so small that it could stay in intestines and go out with not digested food. In intestines we have a big ekosistem which is able to manage our feel of hungar or dissolve chemicals - use for nutrients. So on empty stomach. It is proven.

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Hurtlocker

What about a patch like HRT!@@, that could help people who get stomach probs and the levo goes straight into bloodstream!!pharma who comes up with that is gonna be a hero...not many fillers needed!!!think about it.

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helvella
helvellaAdministrator
in reply to Hurtlocker

I am not convinced that levothyroxine can get through skin which precludes a simple patch.

But there are upcoming patches for other substances which are a bit like one side of Velcro - loads of micro-needles. So I would not dismiss the possibility.

I'd also be concerned at the high dose of levothyroxine that the skin would be exposed to.

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TSH110
TSH110
in reply to helvella

Sounds a tad scratchy....what might happen to the overtreated skin?

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SilverAvocado

At the moment we have highly exposed digestive tracts, though. Doesn't one of the good patient writers talk about that as a big problem and recommend eating with tablets? I can't remember the name, though.

1 like
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helvella
helvellaAdministrator
in reply to SilverAvocado

True - but over much larger area than a square inch or two of a patch. And the highest concentration probably only lasts an hour or two whereas a patch might be on our skin for 24 hours.

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silverfox7

It would have to be easy to administer. Brain fog may make me just take what appeals to me if that was an issue for me.

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TSH110
TSH110
in reply to silverfox7

How about a toothpaste form of thyroid hormones? Not sure how you’d get a dosing system on the tube tho. Good for those who like to split their dose into two smaller ones albeit a tad unevenly spaced!

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Jnetti
Jnetti
in reply to TSH110

Could it be absorbed by smearing on the gums? Mucus membranes are much more absorbent than skin, and better for those with digestion problems

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TSH110
TSH110
in reply to Jnetti

Deffo worth a try I always brush my gums, and my tongue and all the inside of my mouth as well as the teeth 😊

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helvella
helvellaAdministrator
in reply to TSH110

With stripes? :-)

1 like
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silverfox7
silverfox7
in reply to helvella

That could match the football team I support!

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TSH110
TSH110
in reply to silverfox7

HA ha ha I saw helvella’s message on my email and immediately thought Everton mints! Great minds think alike but you posted before me 😉 I am from Merseyside but was a Man U supporter as a child.

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TSH110
TSH110
in reply to helvella

Everton Mint flavoured Levo Toothpaste 😂🤣😂.

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KittyAO

What a great idea to get people thinking about excipients I like the idea of rice paper - no gelatine please for us vegetarians. I like the idea of a spray though too. Hmm decisions, decisions ......

3 likes
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humanbean
humanbean
in reply to KittyAO

I said "gelatine-like" in my answer above because I was thinking of the vegetarians and vegans. Vitamin D supplements in olive oil are sometimes suitable for vegans.

For example, see this : drbvitamins.com/products/ve...

So everyone can be catered for. :)

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Myro
Myro
in reply to KittyAO

Ager ager gelatine? From sea herb.

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helvella
helvellaAdministrator
in reply to Myro

The Wiki article has some other possibilities:

en.wikipedia.org/wiki/Capsu...

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TSH110
TSH110
in reply to Myro

Any iodine in it?

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Myro
Myro
in reply to TSH110

Yas I'm, a fan of iodine. Ager is made from sea herb. But I didn't even had a thought that it can contain iodine. Hardly becouse it is used to grow bacteria in the labs. Iodine will not allow. Your have a bright mind. I'm convicted that iodine level is first thing which has to be fine. Conseqvences are very bad. Especially for girls.

1 like
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silverfox7
silverfox7
in reply to KittyAO

I could easily ‘over dose’ on rice paper though!

1 like
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TSH110
TSH110
in reply to silverfox7

It’s very moreish!

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Jnetti

Gold is probably the most inert substance known. Passes through you unchanged!

Imagine "PANNING" for it though 🤢🤣

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TSH110
TSH110
in reply to Jnetti

You are awful....but I like you!

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Jnetti
Jnetti
in reply to TSH110

And that quote dates you - and me cos of recognising it!!! ;-)

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TSH110
TSH110
in reply to Jnetti

The utterly outrageous Dick Emery no less remember how he’d thump the person and send them flying and that blonde hair and the outfits - brilliant! When he played a man wasn’t it like his mouth was full of marbles?

Here he is in good old black and white:

5 wives!

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humanbean
humanbean
in reply to TSH110

I'd forgotten that Dick Emery made a song out of that!

1 like
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TSH110
TSH110
in reply to humanbean

He released quite a few songs in his time, I think that was the most successful chartwise

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SilverAvocado

Haha, it might be so expensive we'd have to collect our casings on the way out and take them back to the pharmacy to be refilled 😳

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Jnetti

And hire a security guard to collect the prescription!

Would need to be sure it was in a form that disintegrated in the intestine too, or the hormone would just pass all the way through.

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SilverAvocado

Oh yes, the kind of security guard you see outside banks, who handcuff a suitcase to their wrist :p

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Jnetti

:-D

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Sybilla14

Or they put us all on t3 only therapy as the cheaper option 😂

2 likes
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Jnetti
Jnetti
in reply to Sybilla14

What a good idea!!!!! ;-)

1 like
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Myro
Myro
in reply to Jnetti

There was a man with mask and big hammer in Coliseum. Only T3 is hard to manage. Something like insuline. Not pleasant thing.

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helvella
helvellaAdministrator
in reply to Jnetti

You can get gold poisoning!

rarediseases.org/rare-disea...

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Jnetti
Jnetti
in reply to helvella

Didn't know that! Although the stomach does contain strong hydrochloric acid!

en.wikipedia.org/wiki/Aqua_...

Interesting!

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Myro
Myro
in reply to Jnetti

Don't believe anyone or anything even yourself. Check test prove. It could be bacteria, mold, fungus or something else which causing or causing feeling of too much acid in stomach. Try a tea spoon of soda bicarbonate in 200 ml of cold water up to 3 times a day. If not good after one take another one after 10 minutes. Many people say it helps. If you get a hadache it is of toksines from killed enemy. But it happens only in strong attach. Get information of soda bicarbonate to have references.

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TSH110
TSH110
in reply to helvella

Well I never and I thought it was totally inert...perhaps that does not matter 🤔 ....clearly not. Great article 😉

I had a relative who was given gold injections for arthritis and understood it was a lesser of two evils, he died soon after but was in very poor health, he dug his grave with his teeth, as the French say...not to mention a 100 a day fag habit 😱

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Jnetti

Silicon is very inert too.

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Jnetti

Would vitamin C powder be stable enough, or could it be stabilised enough? Many of us take it anyway to help absorption of Levo.

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Myro
Myro
in reply to Jnetti

C vitamin helps with stomach bad feelings. I experienced.

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Fruitandnutcase

I know this is probably a really stupid question but why do the manufacturers have to use fillers or so much filler? Especially if the active ingredient involved is a small % of the actual tablet.

Is it for taste or size or what?

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Jnetti

Not stupid at all, though the answer is a "Why didn't I think of that?!" One.

It's the same sort of reason that gardeners mix really small seeds with fine sand before sowing. Poppies for example. It would be impossible to sow such tiny things one by one like you would with beans.

The amount of hormone we need is far, far tinier than that, you would need a good microscope to even see. So it has to be mixed with something else

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TSH110
TSH110
in reply to Jnetti

Cool answer I just crush the seed pods and let the seeds blow out or let nature disperse them we did do sand and seed sowing at hort college. I thought the fillers were making my NDT slow release...maybe some do...but It never occurred to me the that the active ingredients were so small they needed a carrier. You learn something new everyday and here it can be lots of things!

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Jnetti
Jnetti
in reply to TSH110

I think it only occurred to me when someone asked why Levo can't be prescribed in liquid form. The answer was that it would be impossible to guarantee the right dose because the amount of hormone needed are so tiny

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Fruitandnutcase

I suppose liquid form could be made up in (gelatine?) capsule form like some vitamins and headache meds are

1 like
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helvella
helvellaAdministrator
in reply to Fruitandnutcase

Which is what Tirosint is. But they use glycerol - which some people don't tolerate very well.

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Jnetti

Just thought of carbon. It can be in so many forms it would do for both filler and shell and unlikely to irritate the gut.

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TSH110
TSH110
in reply to Jnetti

Doesn’t it inactivate many drugs - mind you I was thinking of charcoal which is probably something completely different to carbon and is used even now when overdosing has occurred.

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Jnetti
Jnetti
in reply to TSH110

Yes, it couldn't be activated charcoal, but I'm sure there must be a form of charcoal that isn't like that.

Though I don't know that much about chemistry

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TSH110
TSH110
in reply to Jnetti

You know a lot more than me 😊 - I had forgotten ‘Hello Honky Tonks!’ And the mouth marbles was his vicar character

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Jnetti
Jnetti
in reply to TSH110

I didn't say that, thought you did! :-)

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helvella
helvellaAdministrator
in reply to Jnetti

Diamond?

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Jnetti
Jnetti
in reply to helvella

Too hard perhaps

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Nanaedake

The one problem with rice paper dots could be if it was affected by moisture. Levothyroxine potency is affected by moisture. One of the reasons we're advised not to remove from packaging.

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Jnetti
Jnetti
in reply to Nanaedake

Some kind of harmless varnish to protect them?

2 likes
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Sybilla14
Sybilla14
in reply to Jnetti

Chocolate?

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Ellie-Louise

Neck cream, rub it in once a day and forget it. Lol

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Jnetti
Jnetti
in reply to Ellie-Louise

Can't be absorbed through the external skin, needs to go direct to the bloodstream, via the intestinal tract. That probably includes the mouth though.

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ballie52

Would be great as a throat spray that does one pump at a time!😄spray and go!🤣🤣

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Jnetti
Jnetti
in reply to ballie52

But remember, under your armpits would not work and might not smell good either

1 like
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ballie52
ballie52
in reply to Jnetti

🤣🤣🤣

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helvella
helvellaAdministrator
in reply to ballie52

Afraid I don't actually see why a spray would be any better than a tablet, capsule or whatever?

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Jnetti
Jnetti
in reply to helvella

absorption directly into the bloodstream. Maybe under the tongue like a heart spray

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helvella
helvellaAdministrator
in reply to Jnetti

I suspect that the majority will be swallowed with saliva. However, I am absolutely not an expert in absorption so would appreciate if anyone has any clear evidence as to the efficacy of spray levothyroxine.

"GTN" under-tongue spray is indeed readily absorbed but also the dose is not critical.

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TSH110
TSH110
in reply to helvella

I have searched endlessly for articles on buccal/sublingual absorption of T4 and T3 it looks like no one has ever done any bar one that implies T4 can pass through the oral lining but is indeed a paywall.

google.co.uk/amp/s/www.rese...

Someone said here the molecules are too large to pass through the oral cavity lingings to the blood supply. I presume the stomach lining is somehow different. I can’t find anything to verify this either.

Why some companies (eg acella which has a very interesting instruction leaflet) suggest their NDT is best taken sublingually I don’t know, surely it is based on some testing they must have done on it?

1 like
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silverfox7
silverfox7
in reply to helvella

Since damaging my hand and little movement in my fingers I can’t use a spray plus they actually need a lot of effort!

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TSH110
TSH110
in reply to silverfox7

I think my arthritis is to blame I sometimes really struggle to depress the spray button seems the angles are important. My fingers seem very weak if my hand is bent in any way

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yesendi

I would like mine to be with no allergens of any kind, dark chocolate covered and easy to melt on my mouth so I can enjoy it. YUM!

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Myro

My opinion is that T4 doesn't cause troubles. Troublemakcer is in stomac all time. But tacking T4 dissolved in wather seems to me good idea. So fast dissolving tablet with no things in which T4 could stay. I have to drink any way. Some will stay in glass but every time same almount.

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helvella
helvellaAdministrator
in reply to Myro

Levothyroxine is almost insoluble in water. That seems to be quite a bit of the problem.

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helvella
helvellaAdministrator

Due to various forms of transdermal absorption being mentioned, have had a look at some research.

Seems that, with suitable combinations, it is possible to enhance levothyroxine absorption across the skin. Trouble is, even when it gets through the outer layer, it seems to remain in the skin and not get taken into the bloodstream and circulated.

In vitro permeation of levothyroxine across the skin

Author links open overlay panelCristinaPadulaAlicePappaniPatriziaSanti

doi.org/10.1016/j.ijpharm.2...

Abstract

The aim of this work was to investigate the in vitro transdermal permeation characteristics of sodium levothyroxine, in view of its topical application. Permeation experiments were performed in vitro, using rabbit ear skin as barrier. At the end of the experiments levothyroxine retained in the skin was extracted and quantified by HPLC. The formulations tested were solutions and a commercial cream. The use of dimethyl β-cyclodextrin as solubilizing agent increased to a significant extent levothyroxine solubility, but reduced its skin accumulation. Skin stripping before drug application produced a considerable increase in the amount retained and levothyroxine was found also in the receptor compartment. The application of the commercial cream in occlusive conditions increased to a significant extent drug retention in the skin. In conclusion, levothyroxine skin administration is promising in view of a localized effect, because it was retained in the skin. On the contrary, transdermal administration in view of systemic effect does not represent a concrete possibility.

sciencedirect.com/science/a...

A, so far, unmnetioned route is inhalation. Although this paper is quite positive, I am very sceptical, especially in those who already use inhalation for asthma, nicotine or anything else.

Expert Opin Drug Deliv. 2016;13(2):195-205. doi: 10.1517/17425247.2016.1115012. Epub 2015 Dec 18.

Thyroid hormone (levothyroxine) replacement via the respiratory route by inhalation: in vitro exploratory studies.

Agu RU1, Mactavish J1, K Yeung P1, Imran SA2.

Author information

1 a College of Pharmacy , Dalhousie University , Halifax , Canada.

2 b Division of Endocrinology & Metabolism, Faculty of Medicine , Dalhousie University , Halifax , Canada.

Abstract

OBJECTIVES:

To conduct proof of principle studies that will enable development of noninvasive (respiratory) delivery systems for levothyroxine (T4).

METHODS:

Preformulation (solubility, stability), formulation and biopharmaceutical (in vitro absorption, transport, gene expression) studies were conducted. Calu-3 cell line was used for permeation studies.

RESULTS:

Solubility profiles of T4 were established in aqueous (PBS, HBSS, isotonic saline) and non-aqueous solvents (PEG 400, PEG 600, propylene glycol, glycerine). Transport of the compound across Calu-3 cells suggested involvement of active transport systems. This correlated with expression of thyroxine transporters (MCT8, MCT10, OATP1A2, LAT1 and LAT2) in the cell line. Diffusion characteristics showed significant absorption with no detection of T4 metabolite (triiodothyronine). Formulation studies revealed that stable formulations could be prepared using a combination of aqueous and non-aqueous solvents.

CONCLUSIONS:

Results of the studies indicated that T4 can be absorbed effectively from the respiratory mucosa. Factors affecting stability such as pH and temperature should be taken into account during formulation development of this compound for the respiratory route.

KEYWORDS:

Calu-3; levothyroxine; respiratory delivery; thyroid hormone transporters; thyroid hormones

PMID: 26684066

DOI: 10.1517/17425247.2016.1115012

ncbi.nlm.nih.gov/pubmed/266...

Ellie-Louise Jnetti Hurtlocker Nanaedake SilverAvocado

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Jnetti

Interesting! But how can you tell anything about absorption into the bloodstream if skin is tested in vitro?

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helvella
helvellaAdministrator
in reply to Jnetti

Well, in the strictest sense of detecting it in blood flowing, obviously there are difficulties. But have a look at this paper as well. It is very clear that if you do certain things to enhance the possibility of absorption, those very same things tend to keep the levothyroxine in the skin. As we do not have the full paper (and I don't know how much of that I would understand) we cannot see the precise techniques used.

Int J Pharm. 2009 May 8;372(1-2):12-6. doi: 10.1016/j.ijpharm.2008.12.028. Epub 2008 Dec 31.

Innovative formulations for the delivery of levothyroxine to the skin.

Padula C1, Nicoli S, Santi P.

Author information

1 Dipartimento Farmaceutico, Università degli Studi di Parma, Viale G.P. Usberti 27/A, Parma, Italy.

Abstract

The aim of this work was to realize innovative transdermal formulations containing sodium levothyroxine in view of topical administration. Permeation experiments were performed in vitro, using rabbit ear skin as barrier. At the end of the permeation experiments levothyroxine retained in the skin was extracted and quantified by HPLC. Formulations tested were microemulsions and transdermal films. Microemulsions containing isopropyl myristate and isobutanol were shown to be able to increase levothyroxine solubility by the inclusion in reverse micelles. However, the inclusion in reversed micelles reduced the drug release to a significant extent, and consequently skin retention, compared to aqueous solutions. When the microemulsion was included in the transdermal film, drug retention was increased, probably for the enhancer effect of its excipients. The transdermal film proposed in this work could be an interesting alternative to semisolid formulations for the ease of use and the control in the amount of active applied. Additional benefit can be obtained if the film is used in occlusive conditions.

PMID: 19162148

DOI: 10.1016/j.ijpharm.2008.12.028

ncbi.nlm.nih.gov/pubmed/191...

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TSH110
TSH110
in reply to helvella

Poor rabbit

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