a Department of Physical Chemistry, Faculty of Pharmacy , Collegium Medicum of Bydgoszcz, Nicolaus Copernicus University in Toruń , Bydgoszcz , Poland.
Drug Dev Ind Pharm. 2019 Jul;45(7):1120-1129. doi: 10.1080/03639045.2019.1597104. Epub 2019 Apr 2.
The aim of this study was to explore the possibility of using natural deep eutectic solvents (NADES) as solvation media for enhancement of solubility of sulfonamides, as well as gaining some thermodynamic characteristics of the analyzed systems. Low solubility of many active pharmaceutical ingredients is a well-recognized difficulty in pharmaceutical industry, hence the need for different strategies addressing this problem. Among such strategies, those that are environmentally and economically beneficial are of particular interest. The solubility of sulfanilamide and sulfacetamide in 21 different NADES compositions comprising choline chloride with sugars or sugar alcohols was measured spectrophotometrically. Thermodynamic parameters describing the studied systems were determined using the COSMO-RS computational protocol. All of the considered NADES compositions gave an increase in solubility of the studied sulfonamides, with the highest solubilities obtained for the system comprising choline chloride and glycerol in unimolar proportions, which gave a solubility advantage of 83.7 and 73.8 for sulfanilamide and sulfacetamide, respectively. Theoretical studies indicated that the dissolution of both considered sulfonamides has a low endothermic character, with the lowest enthalpy values obtained for the most optimal, i.e. unimolar, proportions. The non-monotonous trend of enthalpy of dissolution was also discussed in terms of intermolecular interactions. The obtained results show the feasibility of using NADES as solubility enhancers for sulfonamides and encourage for further exploration in this field.
本研究旨在探讨将天然深共晶溶剂（NADES）用作增溶磺酰胺的溶剂的可能性，并获得分析体系的一些热力学特性。许多活性药物成分的低溶解度是制药行业公认的难题，因此需要针对该问题采用不同的策略。在这些策略中，具有环境和经济优势的策略特别受到关注。通过分光光度法测量了磺酰胺和磺胺醋酰在 21 种不同组成的 NADES 中的溶解度，这些 NADES 由氯化胆碱与糖或糖醇组成。使用 COSMO-RS 计算协议确定了描述研究体系的热力学参数。考虑的所有 NADES 组成都增加了研究磺酰胺的溶解度，其中以氯化胆碱和甘油摩尔比为 1 的系统获得的溶解度最高，磺酰胺和磺胺醋酰的溶解度分别提高了 83.7 和 73.8。理论研究表明，两种考虑的磺酰胺的溶解均具有低吸热特性，对于最优化即摩尔比为 1 的比例，获得的焓值最低。还讨论了溶解焓的非单调趋势与分子间相互作用的关系。所得结果表明 NADES 作为磺酰胺增溶剂的可行性，并鼓励在该领域进一步探索。
