Iwata M, Fukami T, Kawashima D, Sakai M, Furuishi T, Suzuki T, Tomono K, Ueda H
Sanofi-Aventis K.K, Tokyo, Japan.
Pharmazie. 2009 Jun;64(6):390-4.
We investigated the enhancement of the solubility of glimepiride (GLM), a poorly water soluble anti-diabetes drug, by cogrinding it with various cyclodextrins (CDs) using a ball mill. The phase solubility profiles of GLM with beta-CD and its derivatives were classified as A(L)-type, indicating the formation of a 1 : 1 stoichiometric water-soluble complex. When GLM crystals were coground with beta-CD using a ball mill for 48 h, the aqueous solubility of GLM increased to approximately 250 microg/mL. The powder X-ray diffraction pattern showed that the peak intensity of crystalline GLM decreased after cogrinding. Endothermic peaks of around 208 degrees C, which were assigned to the fusion of GLM crystals, disappeared in the DSC measurement of the ground mixture. After cogrinding, two sharp peaks assigned to sulfonylurea and benzoyl carbonyl stretching bands varied to broaden the peak to around 1700 cm(-1) in the C=O stretching region. These results suggested the formation of a complex between GLM and beta-CD during cogrinding.
我们使用球磨机将难溶于水的抗糖尿病药物格列美脲（GLM）与各种环糊精（CDs）共研磨，以研究其溶解度的提高情况。GLM与β-环糊精及其衍生物的相溶解度曲线被归类为A(L)型，表明形成了1:1化学计量的水溶性复合物。当使用球磨机将GLM晶体与β-环糊精共研磨48小时后，GLM的水溶性增加到约250μg/mL。粉末X射线衍射图谱显示，共研磨后结晶GLM的峰强度降低。在研磨混合物的DSC测量中，归属于GLM晶体熔融的约208℃的吸热峰消失。共研磨后，归属于磺酰脲和苯甲酰羰基伸缩带的两个尖锐峰在C=O伸缩区域变宽至约1700 cm(-1)。这些结果表明在共研磨过程中GLM与β-环糊精之间形成了复合物。
