Effect of grinding on the solid-state stability of cefixime trihydrate

Abstract

The effect of grinding on the physicochemical properties of cefixime trihydrate was studied by means of X-ray diffraction analysis, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), equilibrium water amounts and color difference measurement ( ΔE). Crystalline cefixime trihydrate was confirmed to change to a non-crystalline solid after 4 h of grinding in a ball mill, since X-ray diffraction peak intensities decreased with increasing grinding time. Dehydration temperature of ground cefixime trihydrate also lowered with increasing grinding time, and the activation energy for dehydration of intact cefixime trihydrate and the samples ground 4 h (amorphous form) were calculated by Kissinger's method to be 72.4 kcal mol and 67.5 kcal mol , respectively. The decreased crystallinity with grinding is considered to be due to an increase of water molecules having greater freedom of movement in the crystal lattice. The overall decomposition of solid-state cefixime trihydrate could be expressed by pseudo first-order reaction, and the crystallinity of the ground sample was estimated by an equation expressing the overall decomposition rate constant; which is the sum of the decomposition in 100% crystalline and in 0% crystalline (amorphous) states. Kinetic studies of discoloration of ground cefixime trihydrate showed an increase in the apparent rate constant for discoloration with the increase in the grinding time.