Prediction of the Synergistic Glass Transition Temperature of Coamorphous Molecular Glasses Using Activity Coefficient Models
Prediction of the Synergistic Glass Transition Temperature of Coamorphous Molecular Glasses Using Activity Coefficient Models
复制标题
使用活性系数模型预测共晶分子玻璃的协同玻璃化转变温度
DOI：
10.1021/acs.molpharmaceut.1c00353
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发表时间：
2021
影响因子：
4.9
通讯作者：
Simon, Sindee L.
中科院分区：
文献类型：
--
作者：
Zhao, Xiao;Cheng, Sixue;Koh, Yung P.;Kelly, Brandon D.;McKenna, Gregory B.;Simon, Sindee L.
分子玻璃的二元可混溶混合物（称为共晶玻璃）的玻璃化转变温度（Tg）通常由于两种组分之间的强相互作用而协同地增加超过对于无热混合物所预期的温度。这种协同相互作用对于共晶药物的配制特别重要，因为分子相互作用和产生的Tg强烈影响抗结晶的稳定性、溶解动力学和生物利用度。目前描述二元体系Tg的组成依赖性的模型，包括Gordon-Taylor、Fox、Kwei和Braun-Kovacs方程，未能使用与实验Δ CP和Δα一致的参数来描述共晶药物的行为。在这里，我们开发了一个强大的热力学方法扩展Couchman和Karasz方法，通过使用活度系数模型，包括双参数Margules，非随机两液体（NRTL），和三后缀Redlich-Kister模型。我们发现，该模型，使用实验值的Δ CP和拟合参数的二元相互作用，成功地描述了观察到的协同升高和拐点的Tg与组成的反应的共晶药物。此外，当使用该模型的关联NRTL版本时，NRTL模型的预测得到了改善。结果报告和讨论四种不同的coamorphous系统：吲哚美辛，格列本脲，吲哚美辛，精氨酸，对乙酰氨基酚，吲哚美辛，和芬维A胺，胆酸。
The glass transition temperature (Tg) of a binary miscible mixture of molecular glasses, termed a coamorphous glass, is often synergistically increased over that expected for an athermal mixture due to the strong interactions between the two components. This synergistic interaction is particularly important for the formulation of coamorphous pharmaceuticals since the molecular interactions and resultingTgstrongly impact stability against crystallization, dissolution kinetics, and bioavailability. Current models that describe the composition dependence ofTgfor binary systems, including the Gordon–Taylor, Fox, Kwei, and Braun–Kovacs equations, fail to describe the behavior of coamorphous pharmaceuticals using parameters consistent with experimental ΔCPand Δα. Here, we develop a robust thermodynamic approach extending the Couchman and Karasz method through the use of activity coefficient models, including the two-parameter Margules, non-random-two-liquid (NRTL), and three-suffix Redlich–Kister models. We find that the models, using experimental values of ΔCPand fitting parameters related to the binary interactions, successfully describe observed synergistic elevations and inflections in theTgversus composition response of coamorphous pharmaceuticals. Moreover, the predictions from the NRTL model are improved when the association-NRTL version of that model is used. Results are reported and discussed for four different coamorphous systems: indomethacin–glibenclamide, indomethacin–arginine, acetaminophen–indomethacin, and fenretinide–cholic acid.