Co-amorphization of drugs has been a promising approach to enhance the apparent solubility and dissolution rate of poorly-water soluble drugs. Nimesulide, a BCS Ⅱ drug, was combined with indomethacin to form three co-amorphous systems at molar ratios of 2:1, 1:1 and 1:2 via quench cooling. The aim of this research was mainly to probe the relationship between physical stability (long-term stability and temperature sensitivity) and intermolecular interaction modes among three co-amorphous systems. The calculated glass transition temperature by the Gordon-Taylor equation shows the presence of intermolecular interactions within co-amorphous systems. FTIR spectra further verify that there are hydrogen bonds and π-π stacking in intermolecular interactions. Specific atomic groups involved in the intermolecular hydrogen bonding were investigated using radial distribution function analysis based on molecular dynamic simulation. Gaussian calculation visually gives dominant molecular aggregate composed of multiple hydrogen bonding modes in co-amorphous systems and explains the stability difference of 1:2>1:1>2:1. Finally, powder dissolution profiles were conducted and the 1:2 system has the greatest dissolution advantage with six-fold improvement of dissolution rate compared with pure NMS.

中文翻译：

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从分子聚集体的角度探讨三个尼美舒利-吲哚美辛共非晶体系的物理稳定性。

药物的共非晶化是提高水溶性差的药物的表观溶解度和溶解速率的一种有前途的方法。尼美舒利是一种BCSⅡ药物，通过消灭冷却，与消炎痛合并以摩尔比为2：1、1：1和1：2形成三个共非晶体系。这项研究的主要目的是探究三个共非晶系统之间的物理稳定性（长期稳定性和温度敏感性）与分子间相互作用模式之间的关系。通过Gordon-Taylor方程计算出的玻璃化转变温度表明，在共非晶体系中存在分子间相互作用。FTIR光谱进一步证实分子间相互作用中存在氢键和π-π堆积。使用基于分子动力学模拟的径向分布函数分析研究了分子间氢键涉及的特定原子团。高斯计算从视觉上给出了共非晶体系中由多个氢键模式组成的主要分子聚集体，并解释了1：2> 1：1> 2：1的稳定性差异。最后，进行了粉末溶出曲线分析，与纯NMS相比，1：2系统具有最大的溶出优势，溶出速率提高了六倍。