Effect of Crystal Forms on the Dissolution Behavior and Bioavailability of Tetracycline, Chlortetracycline, and Oxytetracycline Bases

Abstract

The two crystal forms of tetracycline (TC), chlortetracycline (CTC), and oxytetracycline (OTC) were isolated and characterized by X-ray diffraction, infrared spectroscopy, and thermal analysis. Results of elemental analysis and measurement of water contents indicated that all the crystal forms contained some water molecules. The dissolution behavior of the two forms was determined in water, the simulated gastric fluid, and the simulated intestinal fluid. The crystals prepared from methanol were generally found to exhibit a higher solubility than the crystals from water. In order to determine the effect of crystal forms on the bioavailability of the antibiotics, plasma levels in rabbits and blood levels in rats after intraduodenal administration were compared. The results indicated that crystalline states influence significantly the bioavailability of TC, but not CTC and OTC. The similar results were noted from the data of cumulative amounts of urinary excretion after oral administration of the two forms of TC to human subjects.