I would like to ask what are the main differences between doxycycline HCl and hyclate?

I work in the pharmaceutical/veterinary raw materials industry and some clients are saying that they prefer hyclate because it is more concentrated than HCl, but I have yet to come on any articles confirming this. Is this true?


3 Answers 3


[...]they prefer hyclate because it crystallizes more readily than HCl salt

The principal component is doxycycline - in both cases. The active component is a metabolite.

Doxycycline is an antibiotic and belongs to the tetracyclines (= four rings).

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In order to prepare nice ions that can traverse membranes and pumps by the body easily, pharmaceutics containing amino groups or 'alkaloids' (see the red nitrogen atom in the structure), are often converted to their hydrochloride, citrate, oxalate, bromide etc. salts.

These are salts with the (protonated) pharmaceutical as the cation and chloride as the anion. Salts are water soluble.

Here, the notation for this is doxycycline$\ce{.HCl}$.

The crystallisation is done in a solvent or a mixture of solvents.

When the doxycycline$\ce{.HCl}$ precipitates (=when it forms a solid), molecules of the solvent may get embedded, trapped, or entrained in the crystal structure (but the crystals gets pulverized anyway and re-crystallized).

Note that this is not just a wet solid! There would be little or no absorption in that case.

Exactly this happens when the hyclate is formed during the crystallization of doxycycline hydrochloride in a mixture of water and ethanol.

Hyclate is just an abbreviation for hydrochloride hemiethanolate hemihydrate, which means that each molecule of doxycycline comes with 1 $\ce{.HCl\ }$ and 0.5 $\ce{.CH3CH2OH}$ and 0.5 $\ce{.H2O}$ in the crystal.

Whether it is more concentrated (= more active component in one pill) only depends on the formulation of the respective pharmaceutical companies.

  • $\begingroup$ hi thanks for answering! but can you please explain in simpler terms, sorry but i am having trouble understanding your answer.. so if i understand correctly doxycycline hyclate is just the same as hcl? $\endgroup$
    – robertdi
    Commented Mar 26, 2014 at 9:31
  • $\begingroup$ @user1928162 No, they are not the same. Maybe the answer is more clear now. $\endgroup$ Commented Mar 26, 2014 at 9:58
  • $\begingroup$ I think that crystallisation of pharmaceutically active ingredients is not required for easier indigestion but for better and easier quality control. I’m not sure, though. $\endgroup$
    – Jan
    Commented Jun 20, 2016 at 0:16

I believe the doxycycline hyclate have better absorption than other forms when ingested orally. In the hyclate, the bond between the doxycycline and ethanol breaks in a specific area(middle part if am not mistaken) of the small intestine where there are less Calcium and Magnesium salts, therefore less chelation and more of the compound for which doxycycline was a prodrug available to the capillaries and microvilli to be absorbed along with food and chylomicrons.


hyclate because it is more concentrated than HCl

Looking at on ChEBI it appears that a 1 mole, of "doxycycline hyclate" provides two moles of "doxycycline"1. Compared to "doxycycline HCl" which only provides one 2.

@klaus-dieter already says this above, but I think part of the answer your after is that there is twice the amount of doxycycline when you compare molar quantities of the substances. In reality, the actual strength of drugs is likely to be expressed in mass units, and quite possible based on "doxycycline". E.g. doxycycline (as Hydrochloride) 100 mg or doxycycline (as hylate) 100 mg


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