title: Improved oral absorption of dutasteride via Soluplus®-based supersaturable self-emulsifying drug delivery system (S-SEDDS).
abstract: A novel supersaturable self-emulsifying drug delivery system (S-SEDDS) was formulated to improve the oral absorption of dutasteride (DTS), a 5α-reductase inhibitor that is poorly water-soluble. A supersaturable system was prepared by employing Soluplus(®) (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) as a precipitation inhibitor with a conventional SEDDS vehicle consisted of Capryol™ 90, Cremophor(®) EL and Transcutol(®) HP (DTS:SEDDS vehicle:Soluplus(®)=1.0:67.6:10.0 w/v/w). In an in vitro dissolution test in a non-sink condition, the drug dissolution rate from SEDDS was rapidly increased to 72% for an initial period of 5min, but underwent rapid drug precipitation within 2h, decreasing the amount of drug dissolved to one-seventh of its original amount. On the other hand, S-SEDDS resulted in a slower crystallization of DTS by virtue of a precipitation inhibitor, maintaining a 3 times greater dissolution rate after 2h compared to SEDDS. In an in vivo pharmacokinetic study in rats, the S-SEDDS formulation exhibited 3.9-fold greater area-under-curve value than that of the drug suspension and 1.3-fold greater than that of SEDDS. The maximum plasma concentration of S-SEDDS was 5.6- and 2.0-fold higher compared to drug suspension and SEDDS, respectively. The results of this study suggest that the novel supersaturable system may be a promising tool for improving the physicochemical property and oral absorption of the 5α-reductase inhibitor.
authors.affiliation: College of Pharmacy, Chung-Ang University, 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chung-Ang University, 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors.forename: Dong Woo
authors.initials: DW
authors.lastname: Yeom
authors.affiliation: College of Pharmacy, Chung-Ang University, 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors.forename: Ye Seul
authors.initials: YS
authors.lastname: Song
authors.affiliation: College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 330-714, Republic of Korea.
authors.forename: Ha Ra
authors.initials: HR
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 330-714, Republic of Korea.
authors.forename: Yong Seok
authors.initials: YS
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 330-714, Republic of Korea. Electronic address: kangmj@dankook.ac.kr.
authors.forename: Myung Joo
authors.initials: MJ
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Chung-Ang University, 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, Republic of Korea. Electronic address: ywchoi@cau.ac.kr.
authors.forename: Young Wook
authors.initials: YW
authors.lastname: Choi
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D016503:Drug Delivery Systems; D000068538:Dutasteride / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D004655:Emulsions; D007408:Intestinal Absorption; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011145:Polyvinyls / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D058891:5-alpha Reductase Inhibitors; D004655:Emulsions; D011145:Polyvinyls; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D011092:Polyethylene Glycols; D000068538:Dutasteride
keywords: Bioavailability; Dutasteride; Oral absorption; Soluplus(®); Supersaturable self-emulsifying drug delivery system