Effect of Grinding on the Degree of Crystallinity of Cephalexin Powder

The effect of grinding on the degree of crystallinity of cephalexin (CEX) powder was investigated. The intensities of the X-ray diffraction peaks of crystalline CEX decreased with increasing grinding time in an agate shaker mill, and after 4 h showed the same halo pattern as the noncrystalline solid (NC) obtained by the freeze-drying method. The crystallinity of CEX ground for various times was determined by two X-ray diffraction methods, that is, by the internal standard method using lithium fluoride as the internal standard, and by Hermans method, as well as by the infrared (IR) spectral method, for which standard samples were obtained by physically mixing crystalline monohydrate (phase IV) and NC-H2O. The degree of crystallinity determined by Hermans' method was considerably larger than that determined by the X-ray internal standard method for short grinding times (up to about 1 h), but CEX ground for 3-4 h showed 0% crystallinity by both methods. The crystallinity determined by the IR-spectral method accorded quite well with that determined by the X-ray internal standard method for grinding times up to about 30 min, but remained approximately constant at about 15% for longer grinding times. Thus, the state of noncrystalline CEX produced by grinding differs from that of the material obtained by freeze-drying.