Hancock B C, Shamblin S L, Zografi G
School of Pharmacy, University of Wisconsin-Madison 53706, USA.
Pharm Res. 1995 Jun;12(6):799-806. doi: 10.1023/a:1016292416526.
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.
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.
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.
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.
以吲哚美辛、聚维酮（PVP）和蔗糖作为模型化合物，测量无定形药物固体在其玻璃化转变温度（Tg）以下的分子流动性。
采用差示扫描量热法（DSC）测量无定形样品在低于Tg 16 - 47 K的温度下储存不同时间段后的焓松弛。测量得到的焓变用于计算分子弛豫时间参数。使用热机械分析测量PVP薄膜样品尺寸的类似变化。
对于所有模型材料，在典型药品的保质期内，要使DSC检测到的分子运动可忽略不计，有必要将温度至少冷却至低于实验Tg 50 K。在每种情况下，低于Tg时分子运动的温度依赖性均小于通常报道的高于Tg时的情况，且变化迅速。
在所研究的温度范围内，模型无定形固体处于Tg以上分子流动性非常高的区域和远低于Tg分子流动性非常低的区域之间的过渡区。一般而言，预计玻璃态药物固体在比其玻璃化转变温度低五十度的温度下会经历显著的分子流动性。
