title: Improved supersaturation and oral absorption of dutasteride by amorphous solid dispersions.
abstract: In this study, amorphous solid dispersions containing dutasteride and various excipients, manufactured by spray-drying processes, were characterized to determine the effects on their ability to form supersaturated solutions and to identify the effects of supersaturation on increasing the bioavailability of dutasteride. The excipients included Eudragit E, hydroxypropyl-β-cyclodextrin (HP-β-CD), hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), and polyvinylpyrrolidone (PVP K30). A solid dispersion with Eudragit E displayed a high maximum supersaturation with extended supersaturation, compared with a water-soluble polymer. The maximum concentration and the degree of supersaturation increased in the following order: PVP K30<HP-β-CD=HPC<HPMC<Eudragit E. Oral drug absorption of solid dispersions was obviously higher when compared with micronized raw material and physical mixtures, in the following order: HPC<HPMC<Eudragit E. In fact, the AUC(0→24 h) and C(max) of dutasteride increased with supersaturation concentration. These results suggest that amorphous solid dispersions containing Eudragit E, formed by a spray-drying process, offer enhanced supersaturation characteristics, leading to increased oral absorption of dutasteride.
authors.affiliation: College of Pharmacy, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon 305–764, Republic of Korea.
authors.forename: In-Hwan
authors.initials: IH
authors.lastname: Beak
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Kim
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D058891:5-alpha Reductase Inhibitors / Q000008:administration & dosage* / Q000097:blood* / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D001378:Azasteroids / Q000008:administration & dosage* / Q000097:blood* / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D000068538:Dutasteride; D005079:Excipients / Q000737:chemistry*; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008768:Methylmethacrylates / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D005079:Excipients; D008768:Methylmethacrylates; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C102808:Eudragit-E; D065347:Hypromellose Derivatives; D002482:Cellulose; D008747:Methylcellulose; C008079:hydroxypropylcellulose; D011205:Povidone; D000068538:Dutasteride