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

通过磨削，喷涂干燥和熔化的荷兰样品的过程使ursodeooxycholic酸无形地，粉末X射线衍射具有光晕，并在所有样品上具有毫无疑问的特征。光谱法被认为是从每个无形样品中的湿度吸附和表面的无定形样品中的水分，而不是无定形表面上的湿度。在各种温度下，蒸汽雪橇在各种温度下确定。水蒸气吸附的相对剂量，并吸收了水的20％以上的RH AT40 DERX-RAY衍射仪，配备了湿度控制的样品室，另一个人在另一方面清楚地使三个结晶状态蒸馏出来。通过将钠的2-Pro Panol的结晶剂降化来获得新的多晶型物湿气吸附在多孔添加剂，氨基ID的水蒸气中的作用，水分对搜索过程中严格线性链淀粉的络合的影响，等等。