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Design and Evaluation of Ginkgolides Gastric Floating Controlled Release Tablets Based on Solid Supersaturated Self-nanoemulsifying

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Abstract

Ginkgolides are receptor antagonist of platelet activating factor with great clinical prospect, but its application is limited by its low solubility, short half-life and poor alkaline environment stability. It is difficult to solve these problems with a single drug delivery system. In this study, supersaturated self-nanoemulsifying gastric floating tablets of ginkgolides were developed through the combination of solid supersaturated self-nanoemulsifying drug delivery system (solid S-SNEDDS) and gastric retentive floating drug delivery system (GFDDS) to solve these problems of ginkgolides. Solid S-SNEDDS was prepared by D-optimal mixture design, normalization method and single factor experiment. The properties of solid-S-SNEDDS were studied by TEM, PXRD, FT-IR, SEM and in vitro drug release profile. Then, the optimal formulation of stomach floating tablet was obtained through single factor experiment and center composite design, followed by the study of in vitro release, model and mechanism of release, in vitro buoyancy and kinetics of erosion and swelling. PXRD and FT-IR showed that the drug in solid S-SNEDDS existed in an amorphous manner and formed hydrogen bond with excipients. The results showed that the cumulative release of GA and GB in the optimal tablets was 96.12% and 92.57% higher than the simple tablets within 12 h. The release mechanism of the tablet was skeleton erosion and drug diffusion. In 12 h, the optimal tablets can float stably in vitro and release the drug at a constant rate, with a cumulative release of more than 80%. In summary, the combination of SNEDDS and GFDDS is a promising means to solve the problems of ginkgolides.

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Funding

We are appreciative that this study had been funded by the Open Fund of the National Key Laboratory of Process Control and Intelligent Manufacturing Technology of Traditional Chinese Medicine in 2020 (No. SKL2020Z0206) and the Basic Research Project of Liaoning Provincial Department of Education in 2023 (No: JYTZD2023143).

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  1. Kai Zheng and Jing Zhao have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang, 110016, China

    Kai Zheng, Jing Zhao, Qiuli Wang, Yuyang Zhao, Husheng Yang & Xinggang Yang

  2. Cancer Hospital of China Medical University, No. 44 Xiaoheyan Road, Shenyang, 110042, China

    Lian He

  3. Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Shenyang, 110042, China

    Lian He

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  1. Kai Zheng
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Contributions

KZ: collecting, analyzing the data and writing manuscript; JZ: obtaining, analyzing the experimental data; QW: obtaining data and revising manuscript; YZ: analyzing and interpreting results; HY: investigation and supervision; XY: reviewing and editing manuscript; LH: reviewing and editing manuscript.

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Correspondence to Xinggang Yang or Lian He.

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Zheng, K., Zhao, J., Wang, Q. et al. Design and Evaluation of Ginkgolides Gastric Floating Controlled Release Tablets Based on Solid Supersaturated Self-nanoemulsifying. AAPS PharmSciTech 25, 7 (2024). https://doi.org/10.1208/s12249-023-02717-2

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