Otsuka M, Ofusa T, Matsuda Y
Department of Pharmaceutical Technology, Kobe Pharmaceutical University, Japan.
Drug Dev Ind Pharm. 1999 Feb;25(2):197-203. doi: 10.1081/ddc-100102160.
Systematic polymorphic screening tests were performed using 11 kinds of solvents and 6 kinds of preparation methods, and the three specific modifications of glybuzole (forms I and II and amorphous form) were identified by X-ray diffractometry and differential thermal analysis (DTA). The physicochemical properties of forms I and II and amorphous forms were measured using X-ray diffractometry, differential scanning calorimetry (DSC), thermogravimetry (TG), scanning electron microscopy (SEM), solubility tests, and others. The solubilities of all modifications in JP XII, first and second fluid (pH 1.2 and 6.8, respectively) were evaluated at 37 degrees C. Forms I and II and the amorphous form showed almost equivalent solubilities. Forms I and II were stable polymorphic forms at 0% and 75% relative humidity (RH), respectively, at 40 degrees C for 2 months, but the amorphous form was not stable. The crystallization rates of the amorphous form at 0% and 75% RH at 40 degrees C were estimated by X-ray diffraction analysis based on the Jander equation, and the rate at 0% RH was 364 times slower than that at 75% RH.
使用11种溶剂和6种制备方法进行了系统的多晶型筛选试验，并通过X射线衍射法和差示热分析（DTA）鉴定了格列本脲的三种特定变体（晶型I和II以及无定形）。使用X射线衍射法、差示扫描量热法（DSC）、热重分析法（TG）、扫描电子显微镜（SEM）、溶解度测试等方法测量了晶型I和II以及无定形的物理化学性质。在37℃下评估了所有变体在日本药典第十二版第一液和第二液（pH分别为1.2和6.8）中的溶解度。晶型I和II以及无定形表现出几乎相同的溶解度。在40℃下，晶型I和II分别在相对湿度（RH）为0%和75%时为稳定的多晶型形式，但无定形不稳定。基于扬德方程通过X射线衍射分析估算了无定形在40℃下RH为0%和75%时的结晶速率，在0%RH时的速率比在75%RH时慢364倍。
