Physicochemical Properties and Intestinal Absorption of a Ground Mixture of Chloramphenicol Palmitate with Microcrystalline Cellulose

Abstract

The ground mixtures of chloramphenicol palmitate and microcrystalline cellulose were prepared using Form A (stable form) and Form B (metastable form) chloramphenicol palmitates. In spite of the difference in the original crystal structure, X-ray diffraction and differential scanning calorimetry showed that almost the same micro-dispersed or amorphous state of the drug was obtained by the grinding. Dissolution and enzymatic hydrolysis rates of the drug in the ground mixtures were greater than that of Form A. Enzymatic hydrolysis rate of Form B was as fast as those of the ground mixture, even when its dissolution rate was not very greater than that of Form A. The 4 preparations, Form A, Form B, Form A ground mixture and Form B ground mixture, were administered in a random crossover fashion to 5 human subjects, and drug absorption was assessed from urinary excretion data of the metabolites. After oral administration of the ground mixtures, the drug was better and more uniformly absorbed. Especially, in the case of Form A, 20-fold increase in the amount of drug absorbed was observed by the grinding.