Ito S, Kobayashi Y, Nishimura M, Matsumoto K, Itai S, Yamamoto K
Research Center, Taisho Pharmaceutical Co., Ltd. Saitama, Japan.
J Pharm Sci. 1996 Oct;85(10):1117-22. doi: 10.1021/js9600383.
The effect of pulverization on the dehydration behavior of 2-[(2-methylimidazol-1-yl)methyl]benzo[i]thiochromen-1-one monohydrochloride hemihydrate (GK-128), a newly developed serotonin3 receptor antagonist, was studied using powder X-ray diffraction analysis, thermogravimetry (TG), and differential scanning calorimetry (DSC). The crystalline forms of GK-128 obtained by pulverizing with a jet mill and an agale mortar were each confirmed to be the same as that of intact GK-128, since the powder X-ray diffraction patterns of the two prepared samples were identical with that of intact GK-128. However, after pulverization by jet mill, the dehydration temperature of GK-128 was markedly lowered and the DSC endothermic peak due to dehydration disappeared. The activation energy for dehydration, calculated by the Ozawa method using TG data, decreased with decreasing particle size and/or crystallinity of GK-128 crystals, e.g., the activation energies for dehydration of intact and jet-milled GK-128 were 128.1 and 75.9 kj/mol, respectively. The results of comparison of powder X-ray diffraction patterns of pulverized GK-128 and intact GK-128 and of determination of the crystal structure of GK-128 suggested that water molecules could be removed easily along the c-axis of GK-128 crystals.
使用粉末X射线衍射分析、热重分析（TG）和差示扫描量热法（DSC），研究了粉碎对新开发的5-羟色胺3受体拮抗剂2-[(2-甲基咪唑-1-基)甲基]苯并[i]硫代色烯-1-酮盐酸盐半水合物（GK-128）脱水行为的影响。通过气流粉碎机和玛瑙研钵粉碎得到的GK-128的晶型，经证实均与未粉碎的GK-128相同，因为这两种制备样品的粉末X射线衍射图谱与未粉碎的GK-128的图谱相同。然而，气流粉碎机粉碎后，GK-128的脱水温度显著降低，脱水引起的DSC吸热峰消失。使用TG数据通过小泽法计算的脱水活化能，随着GK-128晶体粒径和/或结晶度的降低而降低，例如，未粉碎和气流粉碎的GK-128的脱水活化能分别为128.1和75.9kJ/mol。粉碎的GK-128与未粉碎的GK-128的粉末X射线衍射图谱比较结果以及GK-128晶体结构的测定结果表明，水分子可以沿着GK-128晶体的c轴轻松去除。
