Oral fast-dissolving films containing lutein nanocrystals for improved bioavailability: formulation development, in vitro and in vivo evaluation
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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.
Key wordsbioavailability Box-Behnken Design lutein nanocrystals oral fast-dissolving films
This work was financially supported from the National Natural Science Foundation of China (81660665).
Compliance with Ethical Standards
All procedures were approved by the Animal Research Ethics Committee, General Hospital of Ningxia Medical University.
Conflict of Interest
The authors declare that they have no conflicts of interest.
- 9.Read AM. Influence of digestion model, product type, and enrichment level on in vitro bioavailability of lutein from high lutein functional bakery products. University of Guelph. 2011.Google Scholar
- 17.Shen CY, Shen BD, Xu H, Bai JX, Dai L, Lv QY, et al. Formulation and optimization of a novel oral fast dissolving film containing drug nanoparticles by box-Behnken design-response surface methodology. Drug Dev Ind Pharm. 2014;40(5):649–56. doi: 10.3109/03639045.2014.884116.CrossRefPubMedGoogle Scholar
- 19.Aslam M, Aqil M, Ahad A, Najmi AK, Sultana Y, Ali A. Application of Box–Behnken design for preparation of glibenclamide loaded lipid based nanoparticles: optimization, in vitro skin permeation, drug release and in vivo pharmacokinetic study. J Mol Liq. 2016;219:897–908. doi: 10.1016/j.molliq.2016.03.069.CrossRefGoogle Scholar
- 29.Shanmugam S, Baskaran R, Balakrishnan P, Thapa P, Yong CS, Yoo BK. Solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine for enhanced bioavailability of highly lipophilic bioactive carotenoid lutein. Eur J Pharm Biopharm. 2011;79(2):250–7. doi: 10.1016/j.ejpb.2011.04.012.CrossRefPubMedGoogle Scholar
- 30.Pandey GS, Kumar R, Sharma R, Singh Y, Teotia UVS. Effects of Maltodextrin and glycerin on mechanical properties of oral fast dissolving film of salbutamol sulphate. IJAPBC. 2014;3(1):199–209.Google Scholar