这项工作研究了由一种活性药物成分(奎宁,乙胺嘧啶,或2-苯基咪唑并吡啶)和可能充当赋形剂的第二种成分(甜菜碱,氯化胆碱,四甲基氯化铵,百里酚,薄荷醇,没食子酸,香兰素,乙酰苯胺,4-羟基苯甲醛,丁香醛,没食子酸丙酯,对羟基苯甲酸丙酯,或丁基化羟基茴香醚),旨在解决药物溶解度方面的挑战,生物利用度,和渗透性。使用热力学模型COSMO-RS进行了初步筛选,将搜索范围缩小到三种有前途的赋形剂(百里酚,没食子酸丙酯,和丁基化羟基茴香醚)。结合三种模型药物与筛选出的辅料,对9个固液平衡(SLE)相图进行了实验测定,并且使用视觉熔融法和差示扫描量热法的组合。在所有九个系统中均观察到与热力学理想性的负偏差。此外,总共发现了四个新的共晶,粉末和单晶X射线衍射技术被用来验证其独特的衍射图案。在SLE图的热力学建模中,还应用了两种COSMO-RS参数化(TZVP和TZVPD-FINE),尽管两者都没有始终如一地提供了更好的描述。
This work studies the formation of deep eutectic solvents formed by one active pharmaceutical ingredient (quinine, pyrimethamine, or 2-phenylimidazopyridine) and a second component potentially acting as an excipient (betaine, choline chloride, tetramethylammonium chloride, thymol, menthol, gallic acid, vanillin, acetovanillone, 4-hydroxybenzaldehyde, syringaldehyde, propyl gallate, propylparaben, or butylated hydroxyanisole), aiming to address challenges regarding drug solubility, bioavailability, and permeability. A preliminary screening was carried out using the thermodynamic model COSMO-RS, narrowing down the search to three promising excipients (thymol, propyl gallate, and butylated hydroxyanisole). Nine solid-liquid equilibrium (SLE) phase diagrams were experimentally measured combining the three model drugs with the screened excipients, and using a combination of a visual melting method and differential scanning calorimetry. Negative deviations from thermodynamic ideality were observed in all nine systems. Furthermore, a total of four new cocrystals were found, with powder and single crystal X-ray diffraction techniques being employed to verify their unique diffraction patterns. In the thermodynamic modelling of the SLE diagrams, two COSMO-RS parametrizations (TZVP and TZVPD-FINE) were also applied, though neither consistently delivered a better description over the other.