Department of Physical Chemistry, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague, Czech Republic.
Faculty of Chemical Engineering, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague, Czech Republic.
Molecules. 2023 Mar 8;28(6):2492. doi: 10.3390/molecules28062492.
In this work, the solid-liquid equilibrium (SLE) of four binary systems combining two active pharmaceutical ingredients (APIs) capable of forming co-amorphous systems (CAMs) was investigated. The binary systems studied were naproxen-indomethacin, naproxen-ibuprofen, naproxen-probucol, and indomethacin-paracetamol. The SLE was experimentally determined by differential scanning calorimetry. The thermograms obtained revealed that all binary mixtures investigated form eutectic systems. Melting of the initial binary crystalline mixtures and subsequent quenching lead to the formation of CAM for all binary systems and most of the compositions studied. The experimentally obtained liquidus and eutectic temperatures were compared to theoretical predictions using the perturbed-chain statistical associating fluid theory (PC-SAFT) equation of state and conductor-like screening model for real solvents (COSMO-RS), as implemented in the Amsterdam Modeling Suite (COSMO-RS-AMS). On the basis of the obtained results, the ability of these models to predict the phase diagrams for the investigated API-API binary systems was evaluated. Furthermore, the glass transition temperature () of naproxen (NAP), a compound with a high tendency to recrystallize, whose literature values are considerably scattered, was newly determined by measuring and modeling the values of binary mixtures in which amorphous NAP was stabilized. Based on this analysis, erroneous literature values were identified.
在这项工作中，研究了四个包含两种可形成共无定形系统（CAM）的活性药物成分（API）的二元体系的固液平衡（SLE）。研究的二元体系是萘普生-吲哚美辛、萘普生-布洛芬、萘普生-普罗布考和吲哚美辛-对乙酰氨基酚。通过差示扫描量热法实验测定了 SLE。得到的热谱图表明，所有研究的二元混合物均形成共晶体系。初始二元结晶混合物的熔化和随后的淬火导致所有二元体系和大多数研究的组成形成 CAM。通过使用受扰链统计关联流体理论（PC-SAFT）状态方程和用于真实溶剂的导体相似性筛选模型（COSMO-RS），在阿姆斯特丹建模套件（COSMO-RS-AMS）中，将实验获得的液相线和共晶温度与理论预测进行了比较。基于所获得的结果，评估了这些模型预测所研究 API-API 二元体系相图的能力。此外，通过测量和建模其中稳定了无定形 NAP 的二元混合物的 值，新确定了具有高重结晶趋势的化合物萘普生（NAP）的玻璃化转变温度（）。基于此分析，确定了错误的文献值。
