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Formulation and Pharmacokinetic Evaluation of a Drug-in-Adhesive Patch for Transdermal Delivery of Koumine

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Abstract

The aim of this study was to develop a suitable drug-in-adhesive patch for transdermal delivery of koumine. Acrylic polymer Duro-Tak® 87-4287, which contains hydroxyl groups, may significantly enhance the skin permeation of koumine from transdermal patches containing 0.93–3.72% koumine. Among permeation enhancers, 10% azone showed the greatest potential and increased the flux of koumine to 1.48-fold that of the control. Therefore, an optimized patch formulation containing 3.72% koumine and 10% azone in Duro-Tak® 87-4287 that offers good physical properties was selected for an in vivo pharmacokinetic study using rats. The maximal plasma drug concentration (Cmax) of koumine after transdermal administration (4 mg/patch) was 25.80 ± 1.51 ng/mL, which was in the range of those after oral administration (3 mg/kg and 15 mg/kg). The time to the maximal concentration (Tmax) and the half-life (t1/2) of the drug with transdermal administration were 3.96 ± 0.46 h and 21.10 ± 1.36 h, respectively, which were longer than those with oral administration. Furthermore, the area under the concentration-time curve (AUC0–72 h) of 898.20 ± 45.57 ng·h/mL for the transdermal patch was much higher than that for oral administration (15 mg/kg). In conclusion, the drug-in-adhesive patch containing koumine provides a steady plasma koumine level and sustained release in vivo and can be an effective means of transdermal delivery for koumine.

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Funding

The research was supported by the Industry-University-Research Cooperation Project of Fujian Province (grant number 2017Y4007), the Drug Innovation Major Project of China (grant number 2018ZX09711001-003-024), the Central Financial Support Universities Funds of China (grant number 2018L3008), and the Joint Funds for the Innovation of Science and Technology of Fujian Province (grant number 2018Y9074).

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Authors and Affiliations

  1. Department of Pharmacochemistry, College of Pharmacy, Fujian Medical University, Fuzhou, 350122, Fujian, People’s Republic of China

    Yanping Su & Wenxiang Lu

  2. Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, 350122, Fujian, People’s Republic of China

    Xiaoling Fu, Ying Xu, Jian Yang, Huihui Huang & Changxi Yu

  3. Fujian Center for Safety Evaluation of New Drug, Fujian Medical University, Fuzhou, 350122, Fujian, People’s Republic of China

    Lixiang Ye

  4. Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Fuzhou, 350122, Fujian, People’s Republic of China

    Changxi Yu

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  1. Yanping Su
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Su, Y., Lu, W., Fu, X. et al. Formulation and Pharmacokinetic Evaluation of a Drug-in-Adhesive Patch for Transdermal Delivery of Koumine. AAPS PharmSciTech 21, 297 (2020). https://doi.org/10.1208/s12249-020-01793-y

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