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Effects of crystallinity and surface energetic of solid pharmaceuticals on the interaction with moisture

固体药物结晶度和表面能对与水分相互作用的影响

基本信息

批准号：
09672184
负责人：
OGUCHI Toshio
金额：
$ 0.32万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

Ursodeoxycholic acid was amorphised by the processes of grinding, spray-drying and melt-quenching, and the physico-chemical properties of the amorphous samples were characterised Powder X-ray diffraction gave halo pattern, characteristcs of amourphous state, for all the samples. Since significant difference was observed on thermal analysis and solid-state NMR spectroscopy, however, the microscopic structure was considered to be different from each amourphous sample. From the comparison in the moisture sorption isotherm and surface area among the amorphous samples, it was concluded that water molecules not only adsorbed on the amorphous surface, but penetrated into the interior of the amorphous sampls. In order to estimate the energetics of sorption process, differential heat of sorption was calculated from water vapor sorption profiles determined at various temperatures through the Clausius-Clapeyron equation. Although different water vapor sorption isotherms were obtained for each amo … More rphous sample, it is interestingly found that the profiles of different heat of sorption were almost the same among the three amorphous samples.Sodium cromoglycate gave a gentle increase in water content against an increase of relative humidity on the water vapor sorption isotherm, and absorbs more than 20% of water by humidifying under 90% RH at 40ﾟC.By means of powderX-ray diffractometer equipped with a humidity-controlled sample chamber, three crystalline states were clearly distiguished by different hydration states. On the other hand, a new polymorph was obtaind by crystallinsation of sodium cromoglycate using 2-propanol as a poor solvent. This new crystals gave a step-wise water vapor sorption isotherm, and four crystal forms, at least, were found to exist corresponding to individual steps of the isotherm.Moreover, remarkable results were obtained for moisture effects on crystallisation of amorphous drug, roles of moisture for drug adsorption on porous additives, water vapor sorption characteristics of ground sample of amino acid, effects of moisture on complexation of strictly linear amylose during the process of sealed-heating, etc. Less

采用研磨、喷雾干燥、熔融淬火等方法对熊去氧胆酸进行了非晶化处理，并对非晶样品的理化性质进行了表征。然而，由于热分析和固体核磁共振谱的差异显著，因此认为每个非晶样品的微观结构不同。通过对非晶样品的吸湿等温线和比表面积的比较，得出了水分子不仅吸附在非晶表面，而且渗透到非晶样品内部的结论。为了估计吸附过程的能量学，利用克劳修斯-克拉珀龙方程计算了不同温度下水蒸气吸附曲线的吸附微分热。不同非晶态样品的水蒸气吸附等温线不同，但有趣的是，三种非晶态样品的不同吸附热曲线几乎相同。在水蒸气吸附等温线上，随着相对湿度的增加，甘露糖酸钠的水分含量会缓慢增加，在40ºC、90%相对湿度的条件下，甘露糖酸钠可以吸附20%以上的水分。通过配备湿度控制样品室的粉末x射线衍射仪，通过不同的水化状态可以清楚地区分出三种晶体状态。另一方面，以2-丙醇为不良溶剂，通过异糖酸钠结晶得到了一种新的晶型。这种新晶体给出了一个阶梯式的水蒸气吸附等温线，并且发现至少有四种晶体形式与等温线的各个步骤相对应。此外，水分对非晶态药物结晶的影响、水分对多孔添加剂对药物吸附的作用、氨基酸研磨样品的水蒸气吸附特性、水分对密封加热过程中严格线性直链淀粉络合的影响等方面也取得了显著的结果。少