Effect of Grinding on the Transformations of Polymorphs of Chloramphenicol Palmitate

抄録

The effect of grinding in an agate centrifugal ball mill on the transformations of polymorphs of chloramphenicol palmitate (CPP) were studied by means of X-ray diffraction analysis, infrared (IR) spectroscopy and differential scanning calorimetry (DSC). Three kinds of the polymorphs of CPP were reported, that is, forms A, B and C. There was no change in the X-ray diffraction profile of form A (stable form) on grinding for 600 min, but its profile became broader than that of intact form A. There was no change in the X-ray diffraction profile of form B (meta-stable form) on grinding for 130 min, but form B was transformed into form A by grinding for more than 140 min. Form B ground for 140 min contained about 35% form A ; when ground for 150 min, it contained about 80% form A, and when ground for more than 150 min, it contained a constant level of about 80% form A. The X-ray diffraction profile of form C (meta-stable form) suggested that form C was transformed into form B by grinding for 20 min ; thereafter the product was transformed into form A by grinding for 160 min. Form C ground for 4 min contained about 60% form B ; when ground for 20 min, it contained about 100% form B, and ground for 160 min, it contained about 80% form A. These results suggest that the transformations of polymorphs of CPP by grinding are form C→form B→form A. The melting point (mp) and the heat of fusion (H) were measured by DSC. The mp and the H of form A obtained by grinding were about 2.5°C and about 2.5 kcal/mol lower than those of intact form A, respectively, and the solubility in 50% (v/v) aqueous isopropyl alchohol was about twice that of intact form A.