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

熊去氧胆酸经研磨、喷雾干燥和熔融猝灭等过程进行了非晶化处理，并对非晶态样品的物化性质进行了表征。粉末X-射线衍射仪给出了所有样品的晕图，具有非晶态的特征。然而，由于在热分析和固体核磁共振谱上观察到了显著的差异，因此认为每个非晶样品的微观结构都不同。通过对非晶态样品的吸湿等温线和比表面积的比较，得出结论：水分子不仅吸附在非晶态样品表面，而且渗透到非晶态样品的内部。为了估算吸附过程的能量学，用Clausius-Clapeyron方程从不同温度下测定的水蒸气吸附剖面计算了微分吸附热。虽然每个AMO…的水蒸气吸附等温线不同在水蒸气吸附等温线上，随着相对湿度的增加，色甘酸钠的吸湿量略有增加，在40ﾟC、相对湿度为90%的相对湿度下，吸水率可达20%以上。另一方面，以异丙醇为不良溶剂，对色甘酸钠进行晶化，得到了一种新的晶型。这种新晶体的水蒸气吸附等温线呈阶梯式，至少存在4种晶型，分别对应于该等温线的各个步骤。此外，在水分对无定形药物结晶的影响、水分对药物吸附的作用、多孔性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的直链淀粉络合的影响等方面都取得了显著的结果

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