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Oral fast-dissolving films containing lutein nanocrystals for improved bioavailability: formulation development, in vitro and in vivo evaluation

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Abstract

Lutein is widely used as diet supplement for prevention of age-related macular degeneration. However, the application and efficacy of lutein in food and nutritional products has been hampered due to its poor solubility and low oral bioavailability. This study aimed to develop and evaluate the formulation of oral fast-dissolving film (OFDF) containing lutein nanocrystals for enhanced bioavailability and compliance. Lutein nanocrystals were prepared by anti-solvent precipitation method and then encapsulated into the films by solvent casting method. The formulation of OFDF was optimized by Box-Behnken Design (BBD) as follows: HPMC 2.05% (w/v), PEG 400 1.03% (w/v), Cremophor EL 0.43% (w/v). The obtained films exhibited uniform thickness of 35.64 ± 1.64 μm and drug content of 0.230 ± 0.003 mg/cm2 and disintegrated rapidly in 29 ± 8 s. The nanocrystal-loaded films with reconstituted particle size of 377.9 nm showed better folding endurance and faster release rate in vitro than the conventional OFDFs with raw lutein. The microscope images, thermograms, and diffractograms indicated that lutein nanocrystals were highly dispersed into the films. After administrated to SD rats, t max was decreased from 3 h for oral solution formulation to less than 0.8 h for OFDF formulations, and C max increased from 150 ng/mL for solution to 350 ng/mL for conventional OFDF or 830 ng/mL for nanocrystal OFDF. The AUC 0-24h of conventional or nanocrystal OFDF was 1.37 or 2.08-fold higher than that of the oral solution, respectively. These results suggested that drug nanocrystal-loaded OFDF can be applied as a promising approach for enhanced bioavailability of poor soluble drugs like lutein.

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ACKNOWLEDGEMENTS

This work was financially supported from the National Natural Science Foundation of China (81660665).

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Authors and Affiliations

  1. Pharmaceutical Preparation Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China

    Chen Liu

  2. Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia, 750004, China

    Daoxiao Chang, Xinhui Zhang, Hong Sui, Yindi Kong, Rongyue Zhu & Wenping Wang

  3. Ningxia Engineering and Technology Research Center for Modernization of Hui Medicine & Key Lab of Hui Ethnic Medicine Modernization, Ministry of Education, Yinchuan, Ningxia, 750004, China

    Wenping Wang

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  1. Chen Liu
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  2. Daoxiao Chang
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  3. Xinhui Zhang
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  4. Hong Sui
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  5. Yindi Kong
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  6. Rongyue Zhu
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  7. Wenping Wang
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Correspondence to Wenping Wang.

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Ethics Statement

All procedures were approved by the Animal Research Ethics Committee, General Hospital of Ningxia Medical University.

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The authors declare that they have no conflicts of interest.

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Chen Liu and Daoxiao Chang contributed equally to this article as the co-first author.

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Liu, C., Chang, D., Zhang, X. et al. Oral fast-dissolving films containing lutein nanocrystals for improved bioavailability: formulation development, in vitro and in vivo evaluation. AAPS PharmSciTech 18, 2957–2964 (2017). https://doi.org/10.1208/s12249-017-0777-2

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  • DOI: https://doi.org/10.1208/s12249-017-0777-2

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