Sakata Yukoh, Shiraishi Sumihiro, Otsuka Makoto
Healthcare Research Institute, Wakunaga Pharmaceutical Co, Ltd, 1624 Shimokotachi, Kodacho, Takatagun, Hiroshima 739-1195, Japan.
AAPS PharmSciTech. 2005 Oct 26;6(3):E527-35. doi: 10.1208/pt060366.
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.
使用多种动力学方程和物理模型研究了压缩和粉碎对一水肌酸片脱水动力学和硬度的影响。通过差示扫描量热法（DSC）和粉末X射线衍射（PXRD）研究了未粉碎和粉碎片剂的脱水行为。脱水后，未粉碎和粉碎的一水合物片剂的硬度均显著降低。未粉碎和粉碎的一水合物片剂的脱水程度与片剂硬度之间的关系呈直线。结果表明，片剂硬度的降低取决于结晶水的脱水，斜率值表明未粉碎样品的结合能比粉碎样品的结合能更强。通过使用各种固态动力学模型分析等温DSC数据的拟合情况，评估了未粉碎和粉碎的一水合物片剂的脱水动力学。在不同压缩压力下，未粉碎片剂的脱水遵循核的三维生长机制。相比之下，尽管在500和750 kg/cm2下压缩的粉碎一水合物片剂的脱水动力学遵循三维扩散机制，但在1000 kg/cm2下压缩的片剂的脱水动力学遵循核的三维生长机制。PXRD分析表明，粉碎的一水合物粉末的衍射强度明显低于未粉碎粉末的衍射强度。未粉碎的一水合物片剂的（h00）平面的衍射峰和微孔结构分别受到粉碎和压缩力的影响。
