Codeine salts

[Survival0200]

I've noticed there are pretty many codeine salts and I've been thinking what kind differences do they have compared to each other and to codeine base? There's codeine phosphate, codeine phosphate hemihydrate, codeine phosphate sesquihydrate etc. I'd like to know that how much of codeine base is equivalent to e.g. 1 mg of codeine phosphate? Is there some kind of chart where you could see these things?

 

[redeemer]

Yes, look at their molar mass, which is the weight (in grams) of one mole of said substance. One mole is a specific number of molecules, circa 6×10^23 , so this number reflects how much each molecule of the substance weighs.

Anhydrous codeine base weights 299.36 g/mol. Anhydrous codeine phosphate weighs 397.36 g/mol. This means that 1 gram of codeine phosphate is equivalent to:

299.36 / 397.36 = ~0.75 g codeine base

The most significant difference between the base and its various salts is their solubility and, to some extent, their stability, ie. how easily they decompose.

 

[jasoncrest]

Here in France, OTC Codeine is available as "Codeine Resinate", "Codeine Camsilate", "Codeine Phosphate Anhydrous or "Codeine Phosphate hemihydrate".

Does anyone know if there is a difference between Codeine Camsilate, Resinate and Phosphate?

 

[jasoncrest]

I just found this, the equivalence between 4 Codeine salts:

From the stronger to the weaker:
-20mg Codeine Hydrochloride = 17,1mg Codeine
-20mg Codeine Phosphate Hemihydrate = 15,6mg Codeine
-20mg Codeine Phosphate = 14,7mg Codeine
-20mg Codeine Camsilate = 11,9mg Codeine

(I found that on a very reliable site)

 

[Survival0200]

Do you know anything about the following codeine salts? Why they're so special? I just noticed them, because they're C-I in the U.S.

Codeine methylbromide
Codeine-N-oxide

I'm not sure if that -N-oxide is actually a salt ...

 

[jasoncrest]

I'm not sure if that -N-oxide is actually a salt ...

Codeine-N-oxide seems to be a different chemical than Codeine and its salts; it's maybe not a Codeine salt, but another Opioid...
It seems to be also called "Codeigene" or "Genocodeine"

Morphine-N-oxide (also called genomorphine) is a different chemical than Morphine, I think that there is the same difference between Codeine and Codeine-N-oxide...

EDIT: Morphine-N-Oxide, Morphine Methobromide and Codeine-N-oxide (and I think Codeine Methylbromide too) are all "nitrogen morphine derivatives"...

 

[Survival0200]

What are the reasons for a pharmaceutical company to pick a certain salt of codeine? Wouldn't it be easier to just sell all the codeine as anhydrous base or codeine phosphate and not to make some complicated codeine phosphate hemihydrate or codeine phosphate sesquihydrate? 8( I've noticed codein. phosph. hemihydr. being quite popular, why's that?

 

[raybeez]

What are the reasons for a pharmaceutical company to pick a certain salt of codeine? Wouldn't it be easier to just sell all the codeine as anhydrous base or codeine phosphate and not to make some complicated codeine phosphate hemihydrate or codeine phosphate sesquihydrate? 8( I've noticed codein. phosph. hemihydr. being quite popular, why's that?

This probably has to do with a number of factors, including variations in the types of production facility equipment/reagents possessed by manufacturers, local patent laws, and stability of the salt in a given pharmaceutical preperation (i.e. find a salt that isn't chemically incompatible with the other pill components, likely used in other preperations too).

 

[hussness]

Contrary to the language hemihydrates and sesquihydrates are probably easier to create than anhydrates, for certain compounds. Different compounds have different levels of hydroscopicity (if that's a word). An example would be Magnesium Sulfate heptahydrate (Epsom Salt); when heated above a certain temperature it loses water to become some kind of less than heptahydrate. I don't remember the specifics. Suffice it to say that creating a whatever-hydrate for a compound that is stable under those certain conditions doesn't require any serious organic chemistry. It's more of a natural consequence of a certain preparation procedure.

 

[Dancan]

I'd like to reopen this thread to ask a difficult question for the drug polymaths.

Someone commented that the different preparations of codeine have varying solubility levels. Does anyone know whether or not this is true, and how they compare? Especially with regard to codeine phosphate, and codeine phosphate Hemihydrate, the two most readily available in the UK.

Thanks for those equivalence figures Jason, I've saved them now.

 

[rangrz]

would it possible to prepare a codeine salt of barbituric acid, and if so, would it posses both opiate and barbiturate properties?

if the answer is yes, sigma aldrich, here I come.

 

[vecktor]

barbituric acid itself is not active.

 

[immaturepoop]

^ Well acids and bases do combine to form salts of the given compound. But the addition of barbituric acid to codeine base wouldn't have properties of both a barbituate and an opiate because once ingested it would dissolve into its respective ions. And since barbituric acid is not pharmacologically active on its own, this would only produce an opiate effect...

edit: haha well vecktor beat me to it in the simplest of terms! thanks veck!

 

[Limpet_Chicken]

I think codeine barb-5,5-diester salts have been done, its certainly been done for some opiate or other.

Dangerous combination I bet though, going on what veronal did to me.

 

[MurphyClox]

The differences between the codeine-salts affect for example solubility...

The details, taking morphine and codeine as representatives for all active and desired opium alkaloids:

Solubility of codeine:
free base: 1+120 (water), 1+20 (water @100°C), 1+2 (ethanol), 1+25 (acetone), 1+20 (diethylether), 1+5 (DCM
Hydrochloride: 1+30 (water), 1+1 (water @100°C, 1+100 (ethanol), 1+>1000 (acetone), 1+>1000 (diethylether), 1+500 (DCM)
Phosphate: 1+4 (water), 1 + 0,5 (water @100°C), 1+450 (ethanol), 1+>1000 (acetone), 1+>1000 (diethylether), 1+>1000 (DCM)

Solubility of morphine:
free base: 1+>1000 (water), 1+90 (ethanol), 1+600 (acetone), 1+>1000(diethylether), no value given (DCM)
Hydrochloride: 1+25 (water), 1+50 (ethanol), 1+>1000 (acetone), 1+>1000 (diethylether), 1+>1000(DCM)
all values by weight

Taken from another thread here...
That explains for example why they use nearly always codein-(hemi)phosphate in pharmaceuticals.

 

[rangrz]

hmmm...thats more or less what I thought. ah well, was worth asking.

 

[Dancan]

ah ha. Thanks for referencing that. In the UK, all the codeine products I've found are codeine phosphate, and codeine phosphate hemihydrate, so I guess the solubility will be fairly similar.