Wardhana Yoga Windhu, Kurniawansyah Insan Sunan, Rusdiana Taofik
Department of Pharmaceutics and Pharmaceuticals Technology, Faculty of Pharmacy, Universitas Padjadjaran (UNPAD), Jatinangor, Indonesia.
Study Center of Drug Discovery and Drug Development, Faculty of Pharmacy, Universitas Padjadjaran (UNPAD), Jatinangor, Indonesia.
J Adv Pharm Technol Res. 2025 Jul-Sep;16(3):144-150. doi: 10.4103/JAPTR.JAPTR_337_24. Epub 2025 Aug 9.
Deep eutectic solvents (DESs) in pharmaceutical investigations are still largely unknown in terms of safety, environmental acceptability, and practical use. The investigation focus is primarily of attempts to improve solubility is examined using the co-crystallization approach, which follows similar principles to the production of eutectic mixtures. We will look into the eutectic mixture interaction between selected coformers (nicotinamide [NA], isonicotinamide, and citric acid as acceptors of hydrogen bond and atorvastatin calcium trihydrate [ATCH] as donors of hydrogen bond in the DES system, assisted by propylene glycol [PG]). The study found that the optimum interaction in the DES system for ATCH is using NA in PG as a carrier, with evaluation by polarization microscopy, Fourier transform infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC), verifying that the drug and the DES components have formed H-bonds. H-bond interactions had been recognized through FT-IR and DSC, revealing that the DESs with NA coformer can increase ATCH solubility, as shown in the phase diagram. The increase in solubility was fairly considerable, allowing ATCH to dissolve at high concentrations in DESs, with a solubility of 0.158 ± 0.098 mg/mL compared to 0.000597 ± 0.003 mg/mL in water. Thus, it is obtainable to conclude that among the selected coformers, the DES system with the potential for improving the solubility of ATCH is DESs with NA coformer assisted by PG.
在药物研究中，深共晶溶剂（DESs）在安全性、环境可接受性和实际应用方面仍 largely unknown。研究重点主要是尝试采用共结晶方法来提高溶解度，该方法遵循与共晶混合物生产相似的原理。我们将研究选定的共形成物（烟酰胺[NA]、异烟酰胺和柠檬酸作为氢键受体，阿托伐他汀钙三水合物[ATCH]作为DES系统中的氢键供体，并由丙二醇[PG]辅助）之间的共晶混合物相互作用。研究发现，在DES系统中，ATCH的最佳相互作用是使用PG中的NA作为载体，并通过偏光显微镜、傅里叶变换红外光谱（FT-IR）和差示扫描量热法（DSC）进行评估，证实药物与DES成分形成了氢键。通过FT-IR和DSC识别出了氢键相互作用，这表明含有NA共形成物的DESs可以增加ATCH的溶解度，如相图所示。溶解度的增加相当可观，使得ATCH能够在DESs中高浓度溶解，其溶解度为0.158±0.098mg/mL，而在水中为0.000597±0.003mg/mL。因此，可以得出结论，在选定的共形成物中，具有提高ATCH溶解度潜力的DES系统是由PG辅助的含有NA共形成物的DESs。
