title: Preparation of fenofibrate solid dispersion using electrospray deposition and improvement in oral absorption by instantaneous post-heating of the formulation.
abstract: A coaxial electrospray technique was applied to a poorly soluble drug, fenofibrate (FEN), to increase its bioavailability. A particulate core-shell solid dispersion was designed using poly(methacrylic acid-co-methyl methacrylate) (Eudragit L-100) as a shell material and poly(vinyl pyrrolidone) K12-17 as a dispersant for FEN in the core phase. Although 58% of FEN remained in the crystalline state in the electrosprayed formulation, the dissolution behavior was significantly improved due to decrease in particle size, decrease in crystallinity, and increase in dispersion efficiency. The formulation was subjected to post-heating at 100 °C for 30 s to transform the remaining crystals into the amorphous state to further improve the dissolution behavior. Oral bioavailability was also on the order of: heated formulation>intact formulation>crystalline FEN. Instantaneous heating significantly improved the performance of the formulation despite its simple procedure, and thus can be a powerful step to be incorporated in the formulation manufacturing process.
authors.affiliation: Biomaterials Unit, International Center for Materials Nanoarchitectonics, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan. kawakami.kohsaku@nims.go.jp
authors.forename: Kohsaku
authors.initials: K
authors.lastname: Kawakami
authors.forename: Shaoling
authors.initials: S
authors.lastname: Zhang
authors.forename: Rohit Singh
authors.initials: RS
authors.lastname: Chauhan
authors.forename: Narimoto
authors.initials: N
authors.lastname: Ishizuka
authors.forename: Marina
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Masaoka
authors.forename: Makoto
authors.initials: M
authors.lastname: Kataoka
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamashita
authors.forename: Shinji
authors.initials: S
authors.lastname: Sakuma
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods; D011345:Fenofibrate / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D006358:Hot Temperature; D008297:Male; D033362:Powder Diffraction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D011345:Fenofibrate