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Preparation and Evaluation of Diosgenin Nanocrystals to Improve Oral Bioavailability

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ABSTRACT

Diosgenin (DSG), a well-known steroid sapogenin derived from Dioscorea nipponica Makino and Dioscorea zingiberensis Wright, has a variety of bioactivities. However, it shows low oral bioavailability due to poor aqueous solubility and strong hydrophobicity. The present study aimed to develop DSG nanocrystals to increase the dissolution and then improve the oral bioavailability and biopharmaceutical properties of DSG. DSG nanocrystals were prepared by the media milling method using a combination of pluronic F127 and sodium dodecyl sulfate as surface stabilizers. The physicochemical properties of the optimal DSG nanocrystals were characterized using their particle size distribution, morphology, differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy data, and solubility and dissolution test results. Pharmacokinetic studies of the DSG coarse suspension and its nanocrystals were performed in rats. The particle size and polydispersity index of DSG nanocrystals were 229.0 ± 3.7 nm and 0.163 ± 0.064, respectively. DSG retained its original crystalline state during the manufacturing process, and its chemical structure was not compromised by the nanonizing process. The dissolution rate of the freeze-dried DSG nanocrystals was significantly improved in comparison with the original DSG. The pharmacokinetic studies showed that the AUC0–72h and C max of DSG nanocrystals increased markedly (p < 0.01) in comparison with the DSG coarse suspension by about 2.55- and 2.01-fold, respectively. The use of optimized nanocrystals is a good and efficient strategy for oral administration of DSG due to the increased dissolution rate and oral bioavailability of DSG nanocrystals.

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ACKNOWLEDGEMENTS

This study received financial support from the Key Discipline Construction Projects of Higher School, Hebei Province Natural Science Foundation of China (no. H2014406036), Science and Technology Research Key Project of Higher School in Hebei Province (no. ZH2012050), and Science and Technology Research Youth Fund Project of Higher School in Hebei Province (no. QN2015127).

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Authors and Affiliations

  1. Hebei Province Key Laboratory of Research and Development for Chinese Medicine, Chengde Medical College, Chengde, Hebei, 067000, People’s Republic of China

    Cui-zhe Liu, Jin-hua Chang, Lin Zhang, He-fei Xue, Xi-gang Liu & Pei Liu

  2. Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, People’s Republic of China

    Qiang Fu

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  1. Cui-zhe Liu
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  2. Jin-hua Chang
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  3. Lin Zhang
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Correspondence to Cui-zhe Liu or Qiang Fu.

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Liu, Cz., Chang, Jh., Zhang, L. et al. Preparation and Evaluation of Diosgenin Nanocrystals to Improve Oral Bioavailability. AAPS PharmSciTech 18, 2067–2076 (2017). https://doi.org/10.1208/s12249-016-0684-y

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