title: Preparation and pharmaceutical evaluation of acetaminophen nano-fiber tablets: Application of a solvent-based electrospinning method for tableting.
abstract: In this study, we developed nano-fiber-based tablets with acetaminophen (AAP; LogPow=0.51) for controlled-release delivery systems and evaluated in vitro drug dissolution and in vivo pharmacokinetics in rats. Nano-fibers made from methacrylic acid copolymer S (MAC; EUDRAGIT S100) and containing AAP were prepared using a solvent-based electrospinning (ES) method. In vitro dissolution rate profiles of AAP showed tableting pressure-dependent decreases and pH-dependent increases. The results of tablet tracking by X-ray irradiation showed tablets based on MAC nano-fibers did not disintegrate in the upper intestinal lumen and had the properties of a long-term-acting tablet. In addition, the in vitro release profiles of AAP from nano-fiber tablets prepared by dissolving MAC with AAP (NFT), nano-fiber tablets prepared by adsorbing AAP to drug-free MAC nano-fibers (NFTadso), and tablets prepared by adsorbing half the amount of AAP to MAC nano-fibers containing the remaining amount of AAP (NFThalf) showed independent controlled-release aspects of AAP compared with physical mixture tablets (PMT). In vivo pharmacokinetic studies in rats after intraduodenal administration of 14 mg/rat AAP in NFT, NFTadso, and NFThalf demonstrated that all these tablets based on MAC nano-fibers showed sustained-release profiles compared with PMT, and showed ultra-sustained release properties for AAP. These new tablets based on MAC nano-fibers did not disintegrate in the intestine in the lower pH region, and the tablets could regulate the release of AAP in a pH-dependent manner. The ES method is a useful technique to prepare nano-fibers and showed promising results as an oral delivery system for sustained-release regulation.
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Science, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto 610-0395, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Hamori
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Science, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto 610-0395, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Nagano
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Science, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto 610-0395, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Kakimoto
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Science, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto 610-0395, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Naruhashi
authors.affiliation: Department of Pharmacokinetics, Faculty of Pharmaceutical Science, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto 610-0395, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kiriyama
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Science, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto 610-0395, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Nishimura
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Science, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto 610-0395, Japan. Electronic address: nshibata@dwc.doshisha.ac.jp.
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Shibata
mesh_terms: D000082:Acetaminophen / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004333:Drug Administration Routes; D006863:Hydrogen-Ion Concentration; D016018:Least-Squares Analysis; D008689:Methacrylates / Q000737:chemistry; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D011108:Polymers / Q000737:chemistry; D011312:Pressure; D051381:Rats; D012997:Solvents / Q000737:chemistry*; D013607:Tablets; D013997:Time Factors; D014965:X-Rays
chemical_list: D008689:Methacrylates; D011108:Polymers; D012997:Solvents; D013607:Tablets; C008384:methacrylic acid; D000082:Acetaminophen
keywords: Acetaminophen; Controlled release; Electrospinning; Methacrylic acid copolymer S; Nano-fibers; Pharmacokinetics