Effects of Grinding on the Physicochemical Properties of Cephalexin Powder

抄録

The effects of grinding on the physicochemical properties of cephalexin (CEX) were studied by means of water content measurements, differential thermal analysis (DTA), differential scanning calorimetry (DSC), X-ray diffraction analysis and scanning electron microscopy (SEM). The water content of CEX which had been ground for 4h and converted to a noncrystalline state was proportional to relative humidity (RH) in the range of 0-62% RH, and was about 2 mol/mol at 62-82% RH. The water content of intact crystal phase IV was about 1 mol/mol at 20-75% RH, and about 2 mol/mol at 82-95% RH. The X-ray diffraction data indicated that ground CEX remains in the noncrystalline state until it has absorbed more than about 2 mol of water per mol. At 62% RH, the water content of phase IV increased with increasing grinding time due to the conversion to noncrystalline state. The dehydration point of the ground CEX was depressed by up to about 25°C with increasing grinding time, and the decomposition point of the ground products was depressed by up to about 30°C. In general, the physicochemical properties changed rapidly when the crystallinity of the ground product fell below about 25%. The activation energy and mechanism of dehydration were determined by using nonisothermal kinetic analysis (Criado's method). The dehydration of the product ground for 4h (noncrystalline solid) followed first-order kinetics and its activation energy and latent heat were calculated to be 14.83 kcal/mol and 8.31 kcal/mol, respectively. The product ground for 4h was about 2.5 times more soluble than intact phase IV. The dehydration behavior and solubility of the product ground for 4h were different from those of the freeze-dried product, even though both products are in a noncrystalline state.