Jihua Institute of Biomedical Engineering and Technology, Jihua Laboratory, Foshan, 528000, People's Republic of China.
Foshan Hospital of TCM, Foshan, Guangdong, 528000, People's Republic of China.
AAPS PharmSciTech. 2022 Sep 8;23(7):252. doi: 10.1208/s12249-022-02342-5.
Deep eutectic solvents (DESs) based on choline chloride (C) and L-(+)-tartaric acid diethyl ester (L) were prepared and used in transdermal drug delivery system (TDDS). The internal chemistry structure including the formation and changes of hydrogen bonds of choline chloride and L-(+)-tartaric acid diethyl ester DES was characterized via attenuated total reflection Fourier transform infrared (ATR-FTIR) and H nuclear magnetic resonance (H NMR) spectroscopy. The stoichiometric ratio of choline chloride to L-(+)-tartaric acid diethyl ester as well as water content affected the viscosity, glass transition temperature (T), and drug solubility of the DES. The viscosity and glass transition temperature of the DES (CL14) prepared at the ratio of 1:4 of choline chloride to L-(+)-tartaric acid diethyl ester were 1.19 Pa·s and - 44.01°C, respectively, and decreased to 0.10 Pa·s and - 55.31°C when 10% water (CL1410) was added. Taking diclofenac diethylamine (DDEA), the nonsteroidal anti-inflammatory drug as model, drug solubility was as high as 60 mg/ml and 250 mg/ml in CL14 and CL1410, respectively. The cumulative amount of DDEA was 4.63 ± 2.67 μg/cm and 15.27 ± 4.63 μg/cm for CL14 and CL1410, respectively, at 8 h. The mechanism of percutaneous permeability by the DES may be the disturbance of stratum corneum (SC) lipids as well as changes in the protein conformations. CL14 and CL1410 were also verified as low-cytotoxic and nonirritant. Therefore, the DESs studied are promising to be used in drug solubilization enhancement and transdermal drug delivery system.
基于氯化胆碱（C）和 L-（+）-酒石酸二乙酯（L）的深共晶溶剂（DESs）被制备并用于透皮给药系统（TDDS）。通过衰减全反射傅里叶变换红外（ATR-FTIR）和 H 核磁共振（H NMR）光谱对氯化胆碱和 L-（+）-酒石酸二乙酯 DES 的内部化学结构，包括氢键的形成和变化进行了表征。氯化胆碱与 L-（+）-酒石酸二乙酯的比例以及含水量影响 DES 的粘度、玻璃化转变温度（T）和药物溶解度。当添加 10%的水（CL1410）时，以 1:4 的比例制备的 DES（CL14）的粘度和玻璃化转变温度分别为 1.19 Pa·s 和-44.01°C，降低至 0.10 Pa·s 和-55.31°C。以非甾体抗炎药双氯芬酸二乙胺（DDEA）为模型，药物溶解度在 CL14 和 CL1410 中分别高达 60 mg/ml 和 250 mg/ml。在 8 h 时，DDEA 的累积量分别为 CL14 中的 4.63±2.67μg/cm 和 CL1410 中的 15.27±4.63μg/cm。DES 经皮渗透的机制可能是角质层（SC）脂质的干扰以及蛋白质构象的变化。还验证了 CL14 和 CL1410 具有低细胞毒性和非刺激性。因此，所研究的 DES 有望用于药物增溶和透皮给药系统。
