title: Polymer combination increased both physical stability and oral absorption of solid dispersions containing a low glass transition temperature drug: physicochemical characterization and in vivo study.
abstract: The purpose of this study was establishing a solid dispersion formulation containing a low glass transition temperature (T(g)) and poorly water-soluble drug. Drug/polymer blends with differing physicochemical stabilities and oral absorption were prepared from copolyvidone (PVP-VA), polyvinylpyrrolidone (PVP) or hydroxypropylmethylcellulose (HPMC) by a hot melt extrusion. HPMC drastically increased the drug oral absorption property, while PVP-VA or PVP stabilized solid dispersions during storage by increasing the T(g) in proportion to polymer concentration. Experimental T(g) values corresponded closely with theoretical T(g) values; indeed, the T(g) values of solid dispersion with HPMC did not increase significantly compared to the T(g) value for the drug alone. A solid dispersion formulation incorporating two different polymers-HPMC and either PVP-VA or PVP-maintained increased T(g), physicochemical stability, solubility, and bioavailability of the solid dispresions owing to each polymer. These findings suggested that both oral absorption and physicochemical stability of low-T(g) drug will be improved using less amount of solid dispersion of combined two polymers than polymer alone.
authors.affiliation: Pharmaceutical Research and Technology Labs, Astellas Pharma Inc., 180 Ozumi, Yaizu, Shizuoka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sakurai
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sakai
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sako
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Maitani
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D004355:Drug Stability; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D010599:Pharmacokinetics; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D012995:Solubility; D044366:Transition Temperature; D014753:Vinyl Compounds / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D011108:Polymers; D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D065347:Hypromellose Derivatives; D008747:Methylcellulose; D011205:Povidone