Citation: Xia-Lin Dai, Shuang-Shuang Wang, Ling Yang, Jia-Miao Hao, Wei Gao, Tong-Bu Lu, Jia-Mei Chen. Co-amorphization via ionic liquid intermediate: A novel strategy for polyamorphism discovery and property optimization[J]. Chinese Chemical Letters, ;2026, 37(11): 111827. doi: 10.1016/j.cclet.2025.111827 shu

Co-amorphization via ionic liquid intermediate: A novel strategy for polyamorphism discovery and property optimization

a.
School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, China
b.
Institute for New Energy Materials and Low Carbon Technologies, School of Materials Science and Engineering, Tianjin University of Technology, Tianjin 300384, China
c.
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China

chenjiamei@email.tjut.edu.cn

Received Date: 1 July 2025
Revised Date: 9 September 2025
Accepted Date: 11 September 2025
Available Online: 12 September 2025

Figures(4)

Co-amorphous systems (CAMS) effectively enhance the solubility and dissolution of poorly soluble drugs and enable combined formulations with enhanced compatibility. Here, we report a novel ionic liquid intermediate (ILI) strategy for green CAMS preparation, which uses trace water to form an ionic liquid intermediate under mild heating, followed by dehydration to yield co-amorphous products. ILI was applied to produce co-amorphous of vildagliptin and valsartan (VV-ILI), compared to rotary evaporation (VV-RE) and ball milling (VV-BM) products. Characterization revealed three distinct polyamorphs with varied intermolecular interactions. Molecular electrostatic potential and the Artificial Bee Colony algorithm were employed to simulate possible hydrogen bonding modes. All co-amorphous systems decreased the solubility and dissolution rate of vildagliptin while greatly enhancing those of valsartan, with VV-ILI demonstrating the greatest modification. Besides, all systems exhibit well stability under accelerated conditions. Overall, the ILI strategy provides a green, mild, and energy-efficient approach for engineering co-amorphous systems with tailored physicochemical properties.
- Co-amorphous,
- Ionic liquid,
- Green preparation,
- Polyamorphism,
- Dissolution
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沈阳化工大学材料科学与工程学院沈阳 110142