Sciencemadness Discussion Board - Hydrochloride vs non-hydrochloride compounds

Hydrochloride vs non-hydrochloride compounds

xfusion44 - 4-12-2015 at 04:07

Hi!

I'm interested in what's the difference between let's say "ordinary" pyridine and pyridine.hcl?

On wiki, it says that organic bases are reacted with hydrochloric acid, to make hydrochloride salt (to make them soluble in water - for use in let's say pharmaceutical products)... But are thos two compounds different? Do they react differently and are their properties different? So, what if someone would consume pseudoephedrine instead of pseudoephedrine hcl? Am I totally missing something? Hopefully I won't embarass myself by asking that, but it's still better to ask, otherwise I might never know

Best regards!

gdflp - 4-12-2015 at 07:53

Organic amines will react with acids to form salts. Salts have quite different properties such as largely increased melting and boiling points, and good solubility in water. These behaviors are both due to the structure of salts, shown below. Salts are ionic compounds due to the ionic bond formed between the nitrogen and the counterion, hence the ionic behavior of salts such as high melting point etc.

careysub - 4-12-2015 at 09:05

Another aspect of his question was about the effect of consuming a medicine in two different forms.

The difference between a salt and a base can be expected to affect the absorption by the body, since it affects solubility, but the importance of this varies on a case by case basis. The body has mechanisms for absorbing water soluble and fat soluble compounds so both the base and the salt may be absorbed equally well, though by different parts of the digestive tract (and thus at different rates and delays).

Bioavailability of an active drug though is a complex business. Most drugs get modified by the body in various ways, which greatly affect how they act, so there are many exceptions to any general rule. On some occasions the drug may fail to be converted to its active form, or else may be actually destroyed, depending on the details of absorption.

xfusion44 - 5-12-2015 at 01:56

Thanks!

So, my conclusion from reading your posts is that physical properties change and so, the action in body may change.

@careysub

You said that there may be some problems with absorption, but you weren't really sure, whether the two compounds would act differently - so, those two compounds (base and salt) may actually do the same thing?

I see that organic chemistry is not so simple 0_o

If I try to imagine this on inorganic level, I would rather eat the salt: sodium hydroxide vs sodium chloride

Thanks for explanation

careysub - 5-12-2015 at 15:13

Quote: Originally posted by xfusion44

Thanks!

So, my conclusion from reading your posts is that physical properties change and so, the action in body may change.

@careysub

You said that there may be some problems with absorption, but you weren't really sure, whether the two compounds would act differently - so, those two compounds (base and salt) may actually do the same thing?

I see that organic chemistry is not so simple 0_o

If I try to imagine this on inorganic level, I would rather eat the salt: sodium hydroxide vs sodium chloride

Thanks for explanation

The answer is - it depends. Pharmacology is very complicated. Developing medicine formulations can be tricky due to odd interactions with the packaging and delivery.

Consider the bizarre case of Ritonovir, and AIDS drug:
https://en.wikipedia.org/wiki/Ritonavir

This is a drug that exists in two polymorphs (crystal forms), I and II.

I dissolves easily. II does not.

When Ritonovir was brought to market the only form that had ever been seen was I. Years of laboratory research, testing, drug development and initial use, and no one had ever seen form II. Then Ritonovir stopped working, it no longer dissolved, and form II was discovered.

Once form II (cis) appeared they could never get rid of it. Laboratory procedures that made form I years ago, now only made form II or at least form II contaminated product. Plants in different parts of the world all began making form II. Samples in storage, once brought in to the lab turned into form II. Once form II appeared on the planet it seemed to contaminate all the Ritonovir in the world.

(If you have ever read Vonnegut's novel "Cats Cradle" it is like fictional "Ice 9" that freezes the world catalytically.)

So they had to abandon using the drug in capsule or tablet form, only a suspension would work - and that now suddenly needed constant refrigeration to prevent crystallization.

It is believed that the first bit of Form II was created in a fluke set of conditions (supersaturated solution, a degradation product providing a suitable nucleation surface), but one it existed it contaminated the world.

xfusion44 - 7-12-2015 at 00:12

@careysub

Wow, that seems unbeliveable! 0_o

It's just amazing what can happen in world of chemistry.... and we thought that we know a lot - but there is still so many things that we don't know. Thanks for posting that story

woelen - 7-12-2015 at 03:51

Another reason of using the .HCl or .H2SO4 form of amines is that in general the salts have much better shelf life than the free amines. Many amines (especially the ones with multiple -NH2 groups) have a tendency to polymerize or condense or being oxidized by oxygen from air. E.g. ethylene diamine turns brown on storage, when in contact with air. The same is true for many aromatic amines, used as photography developers. With the salts this problem is much less pronounced.

AJKOER - 7-12-2015 at 07:49

Quote: Originally posted by careysub

............

When Ritonovir was brought to market the only form that had ever been seen was I. Years of laboratory research, testing, drug development and initial use, and no one had ever seen form II. Then Ritonovir stopped working, it no longer dissolved, and form II was discovered.

Once form II (cis) appeared they could never get rid of it. Laboratory procedures that made form I years ago, now only made form II or at least form II contaminated product. Plants in different parts of the world all began making form II. Samples in storage, once brought in to the lab turned into form II. Once form II appeared on the planet it seemed to contaminate all the Ritonovir in the world.

(If you have ever read Vonnegut's novel "Cats Cradle" it is like fictional "Ice 9" that freezes the world catalytically.)

So they had to abandon using the drug in capsule or tablet form, only a suspension would work - and that now suddenly needed constant refrigeration to prevent crystallization.

It is believed that the first bit of Form II was created in a fluke set of conditions (supersaturated solution, a degradation product providing a suitable nucleation surface), but one it existed it contaminated the world.

This cannot be true!

Else, an advanced alien civilization in bioengineering could secretly visit a planet rich in resources and conduct numerous field trips involving species abduction and return (to test efficacy), sampling of food sourced (wheat fields, for example), etc. to eventually "remove" the native population.

This would, of course, imply an actual explanation for UFO's and stories of abduction.

And, besides some very smart people decided to send out a deep space probe to announce our presence to the universe!

xfusion44 - 9-12-2015 at 08:04

Quote: Originally posted by woelen

Another reason of using the .HCl or .H2SO4 form of amines is that in general the salts have much better shelf life than the free amines. Many amines (especially the ones with multiple -NH2 groups) have a tendency to polymerize or condense or being oxidized by oxygen from air. E.g. ethylene diamine turns brown on storage, when in contact with air. The same is true for many aromatic amines, used as photography developers. With the salts this problem is much less pronounced.

But it's interesting, how that different form of compound doesn't affect its actions in body (at least not a lot).

careysub - 9-12-2015 at 08:57

Quote: Originally posted by xfusion44

But it's interesting, how that different form of compound doesn't affect its actions in body (at least not a lot).

Not so.

Different forms of a compound can be the difference between being active and being completely inactive in the body.

Compounds broken down by monoamine oxidase for example may be totally inactive in the salt form, absorbed though the gut, but active in the base form absorbed through the mucosal membranes.

chemrox - 9-12-2015 at 12:02

"When Ritonovir was brought to market the only form that had ever been seen was I. Years of laboratory research, testing, drug development and initial use, and no one had ever seen form II. Then Ritonovir stopped working, it no longer dissolved, and form II was discovered.

Once form II (cis) appeared they could never get rid of it. Laboratory procedures that made form I years ago, now only made form II or at least form II contaminated product. Plants in different parts of the world all began making form II. Samples in storage, once brought in to the lab turned into form II. Once form II appeared on the planet it seemed to contaminate all the Ritonovir in the world."

If true this would be one of the more interesting claims I've read in awhile. Any documentation available?

careysub - 9-12-2015 at 13:55

Quote: Originally posted by chemrox

If true this would be one of the more interesting claims I've read in awhile. Any documentation available?

Quite a lot. This occurred in the late 1980s and has been written up repeatedly since.

I linked to the Wikipedia article, which has several relevant references, such as this:
Pharmaceutical Research, June 2001, Volume 18, Issue 6, pp 859-866
'Ritonavir: An Extraordinary Example of Conformational Polymorphism';
John Bauer, Stephen Spanton, Rodger Henry, John Quick, Walter Dziki, William Porter, John Morris.

Just type:
ritonavir polymorph
into Google.

[Edited on 9-12-2015 by careysub]

chemrox - 11-12-2015 at 16:35

AhhHa. This what is called "mu" in Zen circles.