Solid-state characterization of paclitaxel
Solid-state characterization of paclitaxel
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DOI：
10.1021/js9605226
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发表时间：
1997-12-01
影响因子：
3.8
通讯作者：
Burt, HM
中科院分区：
文献类型：
--
作者：
Liggins, RT;Hunter, WL;Burt, HM
本工作的目的是表征无水紫杉醇和二水紫杉醇的固相性质，将紫杉醇I(无水)悬浮在水中24 h，将其转化为紫杉醇2H(2)O。用差示扫描量热仪(DSC)和热重分析(TGA)对这两种形式进行分析，得到25、100和195℃的X射线粉末衍射(XRPD)图谱。紫杉醇2H(2)O的DSC在100℃以下有两个吸热峰，对应于脱水，其固相称为“脱水紫杉醇2H(2)O”。在168℃下，观察到了一个固体-固体转变，在这个转变过程中，脱水的紫杉醇2H(2)O被转化为一种称为紫杉醇I/Am的半结晶材料。固-固转变后，在220度时熔化。紫杉醇的热重分析。2H(2)O在100℃以下表现出相应的两相失重，相当于2摩尔水的重量。紫杉醇I的DSC在220℃熔融前没有转变，热重分析也没有观察到失重现象。紫杉醇I从熔体中猝灭产生无定形紫杉醇，在152度时发生玻璃化转变，XRPD证实了紫杉醇I，紫杉醇。2H(2)O和脱水紫杉醇。2H(2O)O具有不同的晶体结构。紫杉醇I和紫杉醇I/Am的X-射线图谱相似，但在DSC分析中，两种形式的紫杉醇表现不同。紫杉醇I的体外溶出度研究表明，紫杉醇在4h内浓度迅速上升至3mug/m L，12h后浓度降至1mg/m L，与紫杉醇的溶出度相对应。2H(2)O。紫杉醇的溶解度。2H2O为1微克/毫升。数据表明，紫杉醇存在一种二水形式的紫杉醇，它在37度时与水平衡，但在摄氏45度时脱水。
The purpose of this work was to characterize the solid-state properties of anhydrous paclitaxel and paclitaxel dihydrate, Paclitaxel I (anhydrous) was suspended in water for 24 h to convert it to paclitaxel 2H(2)O. Both forms were analyzed by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), X-ray powder diffraction (XRPD) patterns were obtained at 25, 100, and 195 degrees. Dissolution profiles of both forms were obtained in water at 37 degrees over 20 h. DSC of paclitaxel 2H(2)O showed two endothermic peaks below 100 degrees, corresponding to dehydration, The resulting solid phase was termed ''dehydrated paclitaxel . 2H(2)O''. at 168 degrees, a solid-solid transition was observed in which dehydrated paclitaxel 2H(2)O was converted io a semicrystalline material called ''paclitaxel I/am''. The solid-solid transition was followed by melting at 220 degrees. TGA of paclitaxel . 2H(2)O showed a corresponding biphasic weight loss below 100 degrees, which was equivalent to the weight of 2 mol of water. DSC of paclitaxel I showed no transitions before melting at 220 degrees, and no weight loss was observed by TGA. Quenching of paclitaxel I from the melt produced amorphous paclitaxel with a glass transition at 152 degrees, XRPD confirmed that paclitaxel I, paclitaxel . 2H(2)O, and dehydrated paclitaxel . 2H(2)O had different crystal structures. The X-ray patterns of paclitaxel I and paclitaxel I/am were similar, however the two forms of paclitaxel did not behave identically when analyzed by DSC. The bulk dissolution studies with paclitaxel I showed a rapid increase in concentration to 3 mu g/mL in 4 h, which decreased to 1 mu g/mL after 12 h, corresponding to the solubility of paclitaxel . 2H(2)O. The solubility of paclitaxel . 2H(2)O was 1 mu g/mL. The data demonstrate the existence of a dihydrate form of paclitaxel that is the stable form in equilibrium with water at 37 degrees but which dehydrates at temperatures > 45 degrees.