Pharmaceuticals - <Chemical name> HCl - Why HCl?

I’ve noticed many prescription medications have a chemical or generic name of the form <Chemical> HCl. The HCl obviously meaning hydrochloride or something close to that.

Hydrochloric acid, even a weak solution, is not something which obviously sounds good to include in either an oral med or a topical med. And that’s where I run out of chemistry / biochem knowledge.

So what does HCl really mean in this context and why is it commonly seen in this context?

The compound is a base, but has been neutralized with HCl, and therefore is now a salt with chloride as a counter-ion. HCl is volatile, therefore, as the solvent is dried off, excess acid is removed as well.

Pharmaceuticals have pH limits as part of their release criteria to ensure patient safety. I’ve typically seen a range of 4-7, but it can vary depending on delivery method. Gastric acids in the stomach contain HCl and have a pH of around 1-2, with pH 2 been 100 times more concentrated than a pH 4 solution.

Organic molecules can be poorly soluble in water. While the stomach has extremely low pH, you may still have a kinetic solubility issue. I suspect that the hydrochloride salt helps absorption issues by making the molecule itself water soluble.

Along with dealing with the PK issues, many are salts of amines. Making a HCl salt, for instance, will often give greater long-term stability to the molecule (the lone pair of the nitrogen is bound with the salt and isn’t as reactive) and can have other physical effects, such as turning a liquid into a more manageable solid or easing purification. You can have other salts as well, of course, and it doesn’t have to be a strict acid-base interaction. For example, naproxen (Aleve) is sold as naproxen sodium, where the final purification to get a single enantiomer uses a chiral compound to get enantioselective crystallization.

To clarify this a bit alot of organic compounds are kind of goopy. (IE think fats and oils.) That makes them a bit difficult to work with. However all you have to do is remember what an acid/base reaction produces, salt and water. Salts tend to be nice white powders that disolve in water and are easy to work with. (Which makes stuffing them in a pill easier than trying to fill it with gunk.) So react that organic base with an acid and you’ll get the drug in a salt form.

Your body has no problem with this either. When you swallow one of these pills yout body releases the base which is the drug in question. IE you’re freebasing it. (From what I understand it’s similar to free basing cocaine hydrochloride but in that case they’re reacting it with another base to free it. I’m not sure what reaction your body uses to freebase a drug)

And why is dextromethorphan sold as “Dextromethorphan HBr”? Why is it match with hydrobromide instead of hydrochloride?

Thanks all; I learned a bunch. And also a bunch more about how much I don’t know about chemistry. Go Wiki!!!

A related question if I may …

It seems one of the uses of HCl is to adjust the pH downwards to a good (i.e. fairly low) value for stomach absorbtion. The converse, excess acidity, would be more likely to be a problem for a topical or injectable prep.

If the particular bio-active chemical is too acidic, what would be a common alkaline buffer to increase the pH value? And how (or would) that abbreviation appear in the name?
ETA: I wonder if **robert_columbia **asked in effect the same question while I ws typing.

It may not appear in the name at all. Magnesium oxide is often added to aspirin to make buffered aspirin. In the case of aspirin, you don’t want it to dissolve in the stomach, you want it to stay inactive until it gets to the small intestine. Magnesium oxide is what buffers aspirin so it makes it through the stomach acid intact.