MOLECULAR MOBILITY OF AMORPHOUS PHARMACEUTICAL SOLIDS BELOW THEIR GLASS-TRANSITION TEMPERATURES
MOLECULAR MOBILITY OF AMORPHOUS PHARMACEUTICAL SOLIDS BELOW THEIR GLASS-TRANSITION TEMPERATURES
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DOI：
10.1023/a:1016292416526
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发表时间：
1995-06-01
影响因子：
3.7
通讯作者：
ZOGRAFI, G
中科院分区：
文献类型：
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作者：
HANCOCK, BC;SHAMBLIN, SL;ZOGRAFI, G
目的.以吲哚美辛、聚乙烯吡咯烷酮（PVP）和蔗糖为模型化合物，测定药物固体在玻璃化转变温度（Tg）以下的分子迁移率。方法.差示扫描量热法（DSC）用于测量在低于Tg的16-47 K的温度下储存不同时间段后无定形样品的热松弛。测量的焓变被用来计算分子弛豫时间参数。类似的试样尺寸的变化进行了测量PVP膜使用热机械分析。结果对于所有的模型材料，它是必要的冷却到至少50 K低于实验Tg之前，通过DSC检测到的分子运动可以被认为是可以忽略不计的一个典型的医药产品的寿命。在每种情况下，低于Tg的分子运动的温度依赖性小于通常报告高于Tg，并迅速变化。结论.在所研究的温度范围内，模型无定形固体处于Tg以上的非常高的分子流动性和远低于Tg的非常低的分子流动性的区域之间的过渡区中。一般而言，玻璃状药物固体应预期在低于其玻璃化转变温度高达50度的温度下经历显著的分子流动性。
Purpose. To measure the molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures (Tg), using indomethacin, poly (vinyl pyrrolidone) (PVP) and sucrose as model compounds. Methods. Differential scanning calorimetry (DSC) was used to measure enthalpic relaxation of the amorphous samples after storage at temperatures 16-47 K below Tg for various time periods. The measured enthalpy changes were used to calculate molecular relaxation time parameters. Analogous changes in specimen dimensions were measured for PVP films using thermomechanical analysis. Results. For all the model materials it was necessary to cool to at least 50 K below the experimental Tg before the molecular motions detected by DSC could be considered to be negligible over the lifetime of a typical pharmaceutical product. In each case the temperature dependence of the molecular motions below Tg was less than that typically reported above Tg and was rapidly changing. Conclusions. In the temperature range studied the model amorphous solids were in a transition zone between regions of very high molecular mobility above Tg and very low molecular mobility much further below Tg. In general glassy pharmaceutical solids should be expected to experience significant molecular mobility at temperatures up to fifty degrees below their glass transition temperature.