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Many uncharged organic compounds are sold in solid phase with HCl conjugate - e.g. the antihistamine diphenhydramine.HCl or the derivitizing agent pentafluorobenzyl hydroxylamine.HCl, among many others. Assuming the compound will be dissolved at relatively low concentrations in a buffered medium (for instance when a drug enters the bloodstream) the HCl shouldn't have much chemical effect. Why is it there - does it aid crystallization, or perhaps it's leftover from synthesis and is difficult to separate?

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I would also suggest looking at quora.com/Why-are-so-many-drugs-in-hydrochloride-form/answer/… –  bobthejoe Jun 26 '12 at 16:53
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4 Answers

up vote 8 down vote accepted

Does it aid crystallization?

Yes.

All of the drugs that you see as "hydrochlorides" are alkaloids - a class of basic natural products containing one or more amine functional groups. The dimethylamino group in the upper right of the structure of diphenhydramine (below) is a prime example.

enter image description here

Many of these compounds are not crystalline (at best amphorous, at worst waxy or liquid). These compounds are expensive to purify, since the inexpensive method of recrystallization is not an option. Chromatography is an expensive and wasteful process on the industrial scale.

Reacting alkaloids with HCl (or other acids - for example dextromethorphan HBr) usually produces a crystalline compound. These crystalline compounds are easier to purify.

enter image description here

There is a second more important benefit associated with the hydrochloride salts - they have higher bioavailability than the freebases. The freebase is nonpolar and poorly soluble in water. The hydrochloride salt has an ionic group, which increases water solubility.

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The Wikipedia page on hydrochloride says the following:

Converting insoluble amines into hydrochlorides is a common way to make them water- and acid-soluble. This is particularly desirable for substances used in medications. Many pharmaceutical substances are prepared as hydrochlorides so that they may be quickly released in the gastrointestinal tract; the body usually absorbs a hydrochloride within fifteen or thirty minutes. Very often hydrochlorides of amines have longer shelf-lives than their respective free bases.

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The hydrochloride salts of most alkaloids are also more crystalline, and thus easier to purify by crystallization.

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And they are weakly acidic (similar as ammonia chloride is) instead of being rather alkaline. –  Georg Jun 28 '12 at 19:59
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I think another argument for the use of HCl here, as opposed to HF, HI, or HBr, is simply that chloride is physiologically inert in concentrations found in medical drugs, as opposed to the other halogenides. In other words, it won't poison you.

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