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Effect of Chemical Penetration Enhancer-Adhesive Interaction on Drug Release from Transdermal Patch: Mechanism Study Based on FT-IR Spectroscopy, 13C NMR Spectroscopy, and Molecular Simulation

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Abstract

Chemical penetration enhancers (CPEs) are commonly added into transdermal patches to impart improved skin permeation of drug. However, significant unexplained variability in drug release kinetics in transdermal patches is possible as a result of the addition of CPEs; investigations into the underlying mechanisms are still limited. In the present study, a diverse set of CPEs was employed to draw broad conclusions. Solubility parameters of CPEs and acrylate pressure-sensitive adhesive were calculated by molecular dynamics simulation and Fedors group contribution method to evaluate drug-adhesive miscibility. CPE-adhesive interaction was characterized by FT-IR study, 13C NMR spectroscopy, and molecular docking simulation. Results showed that release enhancement ratio (ERR) of CPEs for zolmitriptan was rank ordered as isopropyl myristate > azone > Plurol Oleique® CC497 > Span® 80 > N-methylpyrrolidone > Transcutol® P. It was found that solubility parameter difference (Δδ) between CPE and adhesive was negatively related with ERR. It was proved that hydrogen bonding between CPE and adhesive would increase drug release rate, but only if the CPE showed good miscibility with adhesive. CPE like isopropyl myristate, which had good miscibility with adhesive, could decrease drug-adhesive interaction leading to the release of drug from adhesive.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China [81773665].

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, Liaoning, China

    Zheng Luo, Chao Liu, Peng Quan, Yimeng Zhang & Liang Fang

  2. College of Pharmacy, Beihua University, 3999 East Binjiang Road, Jilin, 132013, Jilin, China

    Zheng Luo

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  1. Zheng Luo
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  2. Chao Liu
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Correspondence to Liang Fang.

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Luo, Z., Liu, C., Quan, P. et al. Effect of Chemical Penetration Enhancer-Adhesive Interaction on Drug Release from Transdermal Patch: Mechanism Study Based on FT-IR Spectroscopy, 13C NMR Spectroscopy, and Molecular Simulation. AAPS PharmSciTech 22, 198 (2021). https://doi.org/10.1208/s12249-021-02055-1

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