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Design of a Long-Acting Rivastigmine Transdermal Delivery System: Based on Computational Simulation

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Abstract

The purpose of our study was using a computational simulation to develop a long-acting patch of rivastigmine (RVS). A range of patch formulations were screened including pressure sensitive adhesive (PSA), pharmaceutical excipients, and controlled release membranes using transfer simulation based on a mathematical model. Diffusion dynamics parameters for simulated operations were acquired through in vitro release tests (IVRT) and in vitro skin permeation tests (IVPT). The mechanism of controlled release was studied by FTIR (Fourier transform infrared), DSC (differential scanning calorimeter) and molecular docking. Results of a rat in vitro permeation profile showed excellent correlation with the in vivo deconvolution profile (R2=0.998). Experiments testified to transfer of RVS at a relatively uniform speed with high skin permeation (2531.2±142.46 μg/cm2) in 72 h. Pharmacokinetic data obtained in vivo also confirmed stable plasma concentrations over 72 h for the optimized patch, and significant prolongation of both Tmax (11.20±1.79 h) and MRT0-t (33.91±5.33 h). Cmax was controlled with AUC0-t (267.34±24.46 h ng/ml), which was closely comparable to parameters of a commercial Exelon® Patch. The successful development of a long-acting patch of RVS thus underscores the potential of computer aided design in a context of promnesic transdermal delivery.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China, China (No.81872827 and No. 81773676), Dalian High Level Talent Innovation Support Plan (No.2019RT14) and the Dongguan City’s Financial Support Plan for Introducing Innovation Team (No.2018607202009).

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Authors and Affiliations

  1. State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, No.2 Linggong Road, Ganjingzi District, Dalian, 116024, Liaoning, China

    Xue Han, Jingchuan Liu, Wei Wang & Qing Wang

  2. Sinopec Beijing Research Institute of Chemical Industry, Beijing, 100013, China

    Jingchuan Liu

  3. Dalian Kexiang Technology Development Co., Ltd., Dalian, 116086, Liaoning, China

    Xiaoyue Hu

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  1. Xue Han
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  2. Jingchuan Liu
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  4. Wei Wang
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  5. Qing Wang
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Correspondence to Qing Wang.

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Han, X., Liu, J., Hu, X. et al. Design of a Long-Acting Rivastigmine Transdermal Delivery System: Based on Computational Simulation. AAPS PharmSciTech 23, 54 (2022). https://doi.org/10.1208/s12249-021-02207-3

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