Why the Hydrochloride Salt?
Akilli
Greetings,
Just a casual look at the generic names of medications shows many
which terminate in "hydrochloride". Is there some reason (solubility?) which
determines the choice of a hydrochloride salt?
This is probably a quite standard procedure in chemistry, but, as a
non-chemist, (just one of my myriad of non-professions) it is something I have
always been curious about, and would appreciate an explanation, or comment upon
my assumptions.
Much Obliged,
Ethan Gross
Eric Lucas
Akilli wrote:
> (solubility?)
Yes. That, and the fact that hydrochloride salts are more stable to air oxidation than free amines.
Just take a look at an old bottle of aniline to see what I mean. And that's not even an electron
rich amine.
Eric Lucas
Bruce Hamilton
aki...@aol.com (Akilli) wrote:
>Greetings,
> Just a casual look at the generic names of medications shows many
>which terminate in "hydrochloride". Is there some reason (solubility?) which
>determines the choice of a hydrochloride salt?
Pharmaceuticals are often available as either the "free" form, or
as a salt. The hydrochloride forms are usually both more water
soluble and stable in formulations than the free form, and
traditionally, recrystallising salts was a common method of
purifying chemicals. One requirement is that chemicals should be
anemable to, and able to withstand, the conditions during
formulation, and many of the "free" forms of chemicals are not
solids and may also react with other components.
For those pharmaceuticals taken orally, the hydrochloride forms
also can't cause significant increases in concentration of
a minor ionic species when encountering the hydrochloric acid
in our stomach, and thus it's easier to exclude such effects
during approval testing if *HCl forms are used.
Although *HCl is common, there still are a lot of other forms
used, depending on the desired properties, eg codeine phosphate.
Bruce Hamilton
Uncle Al
Akilli wrote:
>
> Greetings,
> Just a casual look at the generic names of medications shows many
> which terminate in "hydrochloride". Is there some reason (solubility?) which
> determines the choice of a hydrochloride salt?
> non-chemist, (just one of my myriad of non-professions) it is something I have
> always been curious about, and would appreciate an explanation, or comment upon
> my assumptions.
Free amines are generally air-sensitive (oxidation), rective as
nucleophiles, and low melting. Free-base cocaine has an unfortunate
tendency ro racemize. Amine salts of strong acids are generally
air-stable, inert, and nicely crystalline. HCl is cheap, low equivalent
weight, and non-toxic. In fact, the oceans are filled with chloride.
Mescaline hemisulfate is magnificently crystalline, while the
hydrochloride exhibits no special aesthetics. That's why we have
chemists.
--
Uncle Al Schwartz
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Bill Walker
Akilli wrote:
> Greetings,
> Just a casual look at the generic names of medications shows many
> which terminate in "hydrochloride". Is there some reason (solubility?) which
> determines the choice of a hydrochloride salt?
> This is probably a quite standard procedure in chemistry, but, as a
> non-chemist, (just one of my myriad of non-professions) it is something I have
> always been curious about, and would appreciate an explanation, or comment upon
> my assumptions.
>
> Much Obliged,
> Ethan Gross
There are lots of reasons, and the specific reason for any particular compound
may be any of the below:
1) Physical form.
Many compounds are liquid in the free base form, but the salt is a solid.
It's easier to store, weigh out, handle, etc. and so on.
2) Stability
Lots of amines are reactive, or are at least volatile and stink.
The salt ain't volatile, so it don't stink.
As the salt, the amine can't act as a very good nucleophile and react with
other molecules.
It will also react less with oxygen to form amine oxides.
3) It's nice to get a good sharp melting point to characterize the finished
product, and many HCL salts have a sharp m.p.
4) As you have already observed, solubility is faster.
Other drugs may exist as the salts of very strange compounds.
Most notable are the steroids, the salts of which I am forced to look up in a
reference book.
Things like iron and calcium salts are usually sold with an organic counter ion so
that they don't upset the stomach so much. They also can help the stomach to
absorb it faster (iron and citrate).....
I'm sure there are other reasons, but can't think of any more off the top o' my
head....
I'm sure Uncle Al can gimme some good educatin' as he usually does.....
(thanks Al, I don't care what everybody says about you)