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The effects of compression and pulverization on the dehydration kinetics and hardness of creatine monohydrate tablets were studied using a variety of kinetic equations and physical models. The dehydration behavior of unpulverized and pulverized tablets was investigated by using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). The hardness of both unpulverized and pulverized monohydrate tablets was significantly decreased after dehydration. The relationship between the degree of dehydration and the tablet hardness of both unpulverized and pulverized monohydrate tablets formed a straight line. The results suggest that the reduction in tablet hardness is dependent on the dehydration of crystal water, and the values of the slopes indicate that the bonding energy of the unpulverized sample was stronger than that of the pulverized sample. The dehydration kinetics of the unpulverized and pulverized monohydrate tablets were evaluated by analyzing the fit of the isothermal DSC data using a variety of solid-state kinetic models. The dehydration of the unpulverized tablets at various levels of compression pressure followed the 3-dimensional growth of nuclei mechanism. In contrast, although the dehydration kinetics of pulverized monohydrate tablets compressed at 500 and 750 kg/cm2 followed the 3-dimensional diffusion mechanism, those compressed at 1000 kg/cm2 followed the 3-dimensional growth of nuclei mechanism. The PXRD analysis indicated that the diffraction intensity of the pulverized monohydrate powder was significantly lower than that of the unpulverized powder. The diffraction peaks of the (h00) planes and the micropore structure of the unpulverized monohydrate tablets were affected by pulverization and compression force, respectively.