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The Study of Deep Eutectic Solvent Based on Choline Chloride and l-(+)-Tartaric Acid Diethyl Ester for Transdermal Delivery System

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Abstract

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 1H nuclear magnetic resonance (1H 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 (Tg), 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/cm2 and 15.27 ± 4.63 μg/cm2 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.

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Funding

This study received financial supports from the Key-Area Research and Development Program of Guangdong Province (2020B1111590001), “Dengfeng Plan” High-level Hospital Construction Opening Project of Foshan Hospital of Traditional Chinese Medicine (202000192) and the Youth Innovation Fund of the Jihua Laboratory, China (X201251XL200).

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Author notes

  1. Jianhua Lv and Xiaoyu Ou contributed equally to this work.

Authors and Affiliations

  1. Jihua Institute of Biomedical Engineering and Technology, Jihua Laboratory, Foshan, 528000, People’s Republic of China

    Jianhua Lv, Xiaoyu Ou, Yaru Fang, Mi Wu, Lei Shang, Yunen Liu & Yan Zhao

  2. Shenyang Medical College, Shenyang, 110034, People’s Republic of China

    Lei Shang & Yunen Liu

  3. Foshan Hospital of TCM, Foshan, Guangdong, 528000, People’s Republic of China

    Fanghao Zheng & Kaijun Lei

Authors
  1. Jianhua Lv
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  2. Xiaoyu Ou
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  3. Yaru Fang
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  4. Mi Wu
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  6. Lei Shang
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  8. Yunen Liu
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  9. Yan Zhao
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Contributions

All authors participated in this study and contributed to the conception and design of the study. Material preparation, date collection, and analysis were performed by Jianhua Lv, Xiaoyu Ou, Mi Wu and Yaru Fang. The first draft of the manuscript was written by Jianhua Lv and Lei Shang. Yan Zhao and Yunen Liu supervised the paper and contributed with the data analysis. Kaijun Lei and Fanghao Zheng performed the supplemental experiments and revised the article. All authors have read and approved the final manuscript.

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Correspondence to Lei Shang, Kaijun Lei, Yunen Liu or Yan Zhao.

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Lv, J., Ou, X., Fang, Y. et al. The Study of Deep Eutectic Solvent Based on Choline Chloride and l-(+)-Tartaric Acid Diethyl Ester for Transdermal Delivery System. AAPS PharmSciTech 23, 252 (2022). https://doi.org/10.1208/s12249-022-02342-5

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