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- W2910361577 abstract "A novel amorphous solid dispersion (ASD) of poorly water-soluble nobiletin (Nob) with highly water-soluble methyl hesperidin (MeHes) was developed. Mixtures of Nob and excipients (MeHes, cellulose derivatives, and synthetic polymers) were processed by hot-melt extrusion (HME). Powder X-ray diffraction analysis proved that most of the HME products were fully amorphized. In dissolution studies, Nob-MeHes ASD showed a prominently higher Nob concentration than other HME products with polymeric excipients. Nob concentration upon dissolution of Nob-MeHes ASD was 400 and 7.5 times higher than that upon dissolution of crystalline Nob and a Nob-MeHes physical mixture, respectively. In addition, Nob-MeHes ASD showed good preservation stability for 6 months under an accelerated condition of 40 °C and 80% relative humidity. Permeation studies using a Caco-2 cell monolayer showed that Nob-MeHes ASD markedly increased the amount of Nob transported. In mice, the plasma Nob concentration and accumulated amount of Nob in various tissues drastically increased after administration of Nob-MeHes ASD. This is the first successful application of MeHes, with a relatively low glass-transition temperature, as an excipient for an ASD formulation prepared by hot-melt extrusion. The drastic improvement in Nob concentration with a small-molecule excipient may be an important finding." @default.
- W2910361577 created "2019-01-25" @default.
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- W2910361577 date "2019-03-01" @default.
- W2910361577 modified "2023-10-18" @default.
- W2910361577 title "Development of nobiletin–methyl hesperidin amorphous solid dispersion: Novel application of methyl hesperidin as an excipient for hot-melt extrusion" @default.
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- W2910361577 doi "https://doi.org/10.1016/j.ijpharm.2018.12.092" @default.
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