STUDIES ON ABSORPTION OF EUTECTIC MIXTURE. II. ABSORPTION OF FUSED CONGLOMERATES OF CHLORAMPHENICOL AND UREA IN RABBITS.

Abstract

Thermal analyses of the system of chloramphenicol and urea were carried out both by the thaw-melt and the DTA method. The system gave a phase diagram of simple eutectic type. The eutectic mixture melts at 104°and has a composition of 76% of the antibiotics and 24% of urea by weight. Dissolution rates of ordinary chloramphenicol, and four kinds of samples prepared by mechanical mixing or by fusion of both substances were investigated. Although the eutectic mixture itself did not dissolve rapidly, the fused conglomerate having a weight ratio of 1 : 4 dissolved much more rapidly, and a maximum was observed in its dissolution curve. Such a peculiar dissolution can be attributed to the size reduction of chloramphenicol by the formation of eutectic mixture and the presence of easily soluble primary crystals of urea which have much greater surface available for contact with the surrounding solution. When the fused conglomerate of this composition was administered to rabbits in suspension or capsule form, the antibiotics was absorbed much more rapidly and to a greater extent. High correspondence between dissolution and absorption rate indicates that the absorption of chloramphenicol is largely dependent on the rate of dissolution which is intimately related to the physical state. It is thought that this new form of medication will be effectively applied for therapeutical purpose, when blood concentration should be achieved as rapidly as possible and yet patients can not receive the antibiotics by injection.