Tetracyclines hydrochloride salt solubility

Miyazaki, S., M. Nakano, and T. Arita. 1975. A comparison of solubility characteristics of free bases and hydrochloride salts of tetracycline antibiotics in hydrochloric acid soluticSteem. Pharm. Bull. 23 1197-1204. 

Formation of soluble hydrochlorides of basic drugs does not necessarily result in improved bioavailability as was illustrated by comparative absorption studies of tetracyclines and lincomycin and their salts. " " Tetracycline-free bases gave higher plasma levels than their hydrochloride salts, while lincomycin hydrochloride had a lower bioavailability than the hexadecylsulfa-mate salts. These differences have been attributed to a common ion effect with gastric HCl following oral administration. 

Dmgs, as we have seen, must be in their molecular form before diffusional absorption processes take place. We would expect bases to be more soluble than acids in the stomach, but it is impossible to generalise in this way. Although the basic form of a dmg as its hydrochloride salt should be soluble to some extent in this medium, this is not always so. Indeed the free bases of, for example, chlor-tetracycline, dimethylchlortetracycline and methacycline are more soluble than their corresponding hydrochlorides in the pH range... 

The tetracyclines are amphoteric antimicrobial agents that can form salts with bases or acids (see Chs 1 and 2). Oxytetracycline is a bitter, yellow, odorless crystalline powder. The base is slightly water soluble and the hydrochloride is readily water soluble and is typically administered to horses by slow i.v. injection. It is effective at 5.5 mg/kg once daily for 2 days or more in the treatment of B. equi but is unlikely to completely clear this infection. It is, therefore, used for premunition. Rapid i.v. injection may cause a precipitous drop in blood pressure and collapse owing to the effects of calcium chelation on the myocardium. Intramuscular injection causes objectionable local reactions in horses and should be avoided. Oral administration may be more... 

The tetracycline derivatives are amphoteric substances that can form salts with both acids and bases. Hydrochloride is the most common salt form and is used in a variety of dosage forms, including medicated feeds, soluble powders, tablets and boluses, intrauterine infusions, intramammary infusions, and injections. Because the tetracyclines are relatively inexpensive, they tend to be used as first-line antimicrobials, especially in ruminants and pigs. Uses include... 

Drugs of the tetraeycline group are amphoteric, forming salts with both acids and bases. They are used as parent compounds (e.g., oxytetracycline dihydrate) or as salts (e.g., oxytetracycline hydrochloride). Their lipid solubilities range from moderate (oxytetracycline and chlortetracycline) to high (doxycycline and minocycline), so that they are able to traverse cell membranes moderately or readily. The former two drugs are natural tetracyclines, while the latter two are semi-synthetic. 

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