Development of nobiletin–methyl hesperidin amorphous solid dispersion: novel application of methyl hesperidin as an excipient for hot-melt extrusion

Publication date: Available online 14 January 2019Source: International Journal of PharmaceuticsAuthor(s): Masazumi Iwashita, Kohjiro Hashizume, Masahiro Umehara, Takaaki Ishigami, Shintaro Onishi, Masaki Yamamoto, Kenjirou Higashi, Kunikazu MoribeAbstractA 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 prepa...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research