Abstract
Crystalline cephalexin (CEX) was ground by agate centrifugal ball mill, and the relationship between the physicochemical properties of ground CEX and its degree of crystllinity was studied by means of X-ray diffraction analysis, the infrared (IR) spectral method, thermal analysis (DTA and DSC) and scanning electron microscopy (SEM). The intensities of the X-ray diffraction peaks of crystalline CEX (phase IV) decresased with increasing grinding time in an agate centrifugal ball mill. By grinding for 4hrs showed the same halo pattern as the noncrystalline solid (NC) obtained by the freeze-drying method. The crystallinity of ground CEX was determined by the X-ray diffraction and IR spectral methods. The degree of crystallinity determined by the X-ray diffraction method decreased with increasing grinding time. After 2hrs, it was 0%. At 62% relative humidity, the water content of ground CEX increased with increasing grinding time due to the conversion to a noncrystalline state. The dehydration and decomposition points of ground CEX were depressed with decreasing crystallinity.
The activation energy and mechanism of dehydration were determined by the thermal kinetic method using DSC (Criado's method). The product ground for 4hrs was about 2.5 times more soluble than the intact phase IV. The dehydration behavior and solubility of the product for 4hrs were different from those of the freeze-dried product, even though both products are X-ray diffractometically in a noncrystalline state.
