title: Preparation and in vivo evaluation of a dutasteride-loaded solid-supersaturatable self-microemulsifying drug delivery system.
abstract: The purpose of this study was to prepare a dutasteride-loaded solid-supersaturatable self-microemulsifying drug delivery system (SMEDDS) using hydrophilic additives with high oral bioavailability, and to determine if there was a correlation between the in vitro dissolution data and the in vivo pharmacokinetic parameters of this delivery system in rats. A dutasteride-loaded solid-supersaturatable SMEDDS was generated by adsorption of liquid SMEDDS onto Aerosil 200 colloidal silica using a spray drying process. The dissolution and oral absorption of dutasteride from solid SMEDDS significantly increased after the addition of hydroxypropylmethyl cellulose (HPMC) or Soluplus. Solid SMEDDS/Aerosil 200/Soluplus microparticles had higher oral bioavailability with 6.8- and 5.0-fold higher peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) values, respectively, than that of the equivalent physical mixture. A linear correlation between in vitro dissolution efficiency and in vivo pharmacokinetic parameters was demonstrated for both AUC and Cmax values. Therefore, the preparation of a solid-supersaturatable SMEDDS with HPMC or Soluplus could be a promising formulation strategy to develop novel solid dosage forms of dutasteride.
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Korea. minsookim@pusan.ac.kr.
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Korea. edel@pusan.ac.kr.
authors.forename: Eun-Sol
authors.initials: ES
authors.lastname: Ha
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Korea. jimasd@pusan.ac.kr.
authors.forename: Gwang-Ho
authors.initials: GH
authors.lastname: Choo
authors.affiliation: College of Pharmacy, Kyungsung University, Busan 608-736, Korea. baek@ks.ac.kr.
authors.forename: In-Hwan
authors.initials: IH
authors.lastname: Baek
mesh_terms: D000818:Animals; D003460:Crystallization; D016503:Drug Delivery Systems; D000068538:Dutasteride / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004655:Emulsions / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008855:Microscopy, Electron, Scanning; D011108:Polymers / Q000737:chemistry; D017207:Rats, Sprague-Dawley
chemical_list: D004655:Emulsions; D011108:Polymers; D000068538:Dutasteride
keywords: bioavailability; cellulose; drug delivery; dutasteride; self-emulsifying