Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, 55455, USA.
Pharm Res. 2013 Mar;30(3):714-20. doi: 10.1007/s11095-012-0910-6. Epub 2012 Oct 27.
The work aims at investigating the correlation of water sorption potential with different measures of molecular mobility in an annealed amorphous model compound (trehalose).
Amorphous trehalose, prepared by freeze-drying, was annealed at 100°C (17°C < T (g)) for up to 120 h. Global molecular mobility was studied using a broadband dielectric spectrometer in the frequency range of 10(6)-10(-2) Hz. Enthalpic recovery was measured by differential scanning calorimetry and water sorption profiles were obtained using an automated vapor sorption balance.
As a function of annealing time, there was an increase, both in average α-relaxation time and enthalpic recovery and a decrease in the amount of sorbed water. A strong linear correlation was observed between the water sorption potential and the dielectric relaxation time, indicating a common underlying mechanism of the effect of annealing time on these properties. Enthalpic recovery, which is widely used as a measure of structural relaxation, did not correlate well with the extent of water sorption.
The α-relaxation time can be used as a predictor of the water sorption potential of amorphous trehalose. It will be of interest and value to develop such predictive models for other amorphous compounds of pharmaceutical interest.
本研究旨在探讨在退火无定形模型化合物（海藻糖）中，水吸附潜力与不同分子迁移率测量值的相关性。
通过冷冻干燥制备无定形海藻糖，在 100°C（17°C < T (g)）下退火长达 120 h。使用宽带介电光谱仪在 10(6)-10(-2) Hz 的频率范围内研究整体分子迁移率。通过差示扫描量热法测量焓恢复，使用自动蒸汽吸附平衡获得水吸附曲线。
作为退火时间的函数，平均 α-松弛时间、焓恢复增加，吸附水的量减少。观察到水吸附潜力与介电松弛时间之间存在强烈的线性相关性，表明退火时间对这些性质的影响存在共同的潜在机制。焓恢复广泛用作结构弛豫的度量，但与水吸附的程度相关性不佳。
α-松弛时间可用作预测无定形海藻糖水吸附潜力的指标。为其他具有药用价值的无定形化合物开发此类预测模型将具有重要意义和价值。
