Effect of grinding on the crystallinity and chemical stability in the solid state of cephalothin sodium

Abstract The effects of grinding on the crystallinity of cephalothin sodium, and on the chemical stability of the ground products were investigated by X-ray diffraction, infrared spectra and differential thermal analysis. The X-ray diffraction peaks of all samples decreased after grinding, but the diffraction profiles had no halo pattern. This suggests that part of the cephalothin sodium was converted into a noncrystalline solid. The crystallinity of cephalothin sodium decreased with increased grinding time during the initial grinding process, and cephalothin sodium ground for 2 h was about 30% crystalline. However, the crystallinity increased after grinding for 3–10 h, reaching equilibrium at about 50%. The decomposition point, measured by differential thermal analysis of the ground products, fell rapidly during early grinding, and then decreased from 202 to 187°C after 2 h. However, it rose to 191°C after 3 h and thereafter stayed at approx. 192°C. The water content of intact cephalothin sodium increased at more than 95% relative humidity (R.H.). The water content after grinding for 2 or 10 h increased at more than 93% R.H. The results suggest that the chemical stability in the solid state and the hygroscopicity of cephalothin sodium are closely related to the crystallinity.