A comparison of solubility characteristics of free bases and hydrochloride salts of tetracycline antibiotics in hydrochloric acid solutions.

The pH-solubility profiles of tetracycline antibiotics in HCl-sodium acetate buffer solution were obtained at 37°. Solubility vs. pH curves of chlortetracycline hydrochloride (CTC-HCl) passes through a maximum at approximately 2.8 whereas solubility of tetracycline hydrochloride (TC-HCl) increases with decrease in pH. The similar solubility vs. pH curve was also obtained for demethylchlortetracycline hydrochloride (DMCT-HCl) and methacycline (MOTC-HCl). From the studies on the salts effect on the solubility of the tetracycline antibiotics, the drop at more acidic pH value in pH-solubility profiles of CTC-HCl, DMCT-HCl, and MOTC-HCl was found to be due to the common ion suppression of the solubility product equilibrium. The dissolution behavior of the free base and the hydrochloride of tetracyclines was examined in dilute hydrochloric acid solutions, whose pH ranges from 1.2 to 2.1. The results indicated that the free base of CTC, DMCT, and MOTC was more soluble than the corresponding hydrochloride at the gastric pH values (pH 1.2-1.4 for CTC and DMCT and pH 1.2-2.1 for MOTC). On the other hand, TC-HCl exhibited a greater solubility than the base in pH 1.2 since the solubility of TC-HCl was little affected by addition of common ion (Cl-).