School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Int J Pharm. 2023 Jul 25;642:123181. doi: 10.1016/j.ijpharm.2023.123181. Epub 2023 Jun 24.
As novel green solvents, deep eutectic solvent (DES) with distinct liquid properties has gained increasing interest in pharmaceutical fields. In this study, DES was firstly utilized for improving powder mechanical properties and tabletability of drugs, and the interfacial interaction mechanism was explored. Honokiol (HON), a natural bioactive compound, was used as model drug, and two novel HON-based DESs were synthesized with choline chloride (ChCl) and l-menthol (Men), respectively. The extensive non-covalent interactions were account for DES formation according to FTIR, H NMR and DFT calculation. PLM, DSC and solid-liquid phase diagram revealed that DES successfully in situ formed in HON powders, and the introduction of trace amount DES (99:1 w/w for HON-ChCl, 98:2 w/w for HON-Men) significantly improve mechanical properties of HON. Surface energy analysis and molecular simulation revealed that the introduced DES promoted the formation of solid-liquid interfaces and generation of polar interactions, which increase interparticulate interactions, thus better tabletability. Compared to nonionic HON-Men DES, ionic HON-ChCl DES exhibited better improvement effect, since their more hydrogen-bonding interactions and higher viscosity promote stronger interfacial interactions and adhesion effect. The current study provides a brand-new green strategy for improving powder mechanical properties and fills in the blank of DES application in pharmaceutical industry.
作为新型绿色溶剂，具有独特液体性质的深共熔溶剂（DES）在制药领域引起了越来越多的关注。在本研究中，首次利用 DES 来改善药物的粉末力学性能和可压性，并探讨了界面相互作用机制。厚朴酚（HON）是一种天然生物活性化合物，被用作模型药物，分别用氯化胆碱（ChCl）和薄荷醇（Men）合成了两种新型基于 HON 的 DES。根据 FTIR、H NMR 和 DFT 计算，广泛的非共价相互作用解释了 DES 的形成。PLM、DSC 和固-液相图表明，DES 成功地在 HON 粉末中原位形成，痕量 DES（HON-ChCl 为 99:1 w/w，HON-Men 为 98:2 w/w）的引入显著改善了 HON 的力学性能。表面能分析和分子模拟表明，引入的 DES 促进了固-液界面的形成和产生极性相互作用，从而增加了颗粒间相互作用，进而提高了可压性。与非离子型 HON-Men DES 相比，离子型 HON-ChCl DES 表现出更好的改善效果，因为其具有更强的氢键相互作用和更高的粘度，从而促进了更强的界面相互作用和粘附效应。本研究为改善粉末力学性能提供了一种全新的绿色策略，并填补了 DES 在制药行业应用的空白。
