title: Enhanced dissolution and oral absorption of tacrolimus by supersaturable self-emulsifying drug delivery system.
abstract: A new Soluplus (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer)-based supersaturable self-emulsifying drug delivery system (S-SEDDS) was formulated to enhance oral absorption of tacrolimus (FK506) with minimal use of oil, surfactant, and cosurfactant. A high payload supersaturable system (S-SEDDS) was prepared by incorporating Soluplus, as a precipitation inhibitor, to SEDDS consisting of Capmul MCM, Cremophor EL, and Transcutol (FK506:vehicle:Soluplus =1:15:1). In vitro dissolution profile and in vitro pharmacokinetic aspect of S-SEDDS in rats were comparatively evaluated with those of conventional SEDDS formulas containing four times greater content of vehicle components (FK506:vehicle =1:60). Both formulations formed spherical drug-loaded microemulsion <70 nm in size when in contact with aqueous medium. In an in vitro dissolution test in a nonsink condition, the amphiphilic polymer noticeably retarded drug precipitation and maintained >80% of accumulated dissolution rate for 24 hours, analogous to that from conventional SEDDS. Moreover, pharmacokinetic parameters of the maximum blood concentration and area under the curve from S-SEDDS formula in rats were not statistically different (P>0.05) than those of conventional SEDDS. The results suggest that the Soluplus-based supersaturable system can be an alternative to achieve a comparable in vitro dissolution profile and in vivo oral absorption with conventional SEDDS, with minimal use of vehicle ingredients.
authors.affiliation: College of Pharmacy, Dankook University, Dongnam-gu, Choenan, Chungnam, Korea.
authors.forename: Dae Ro
authors.initials: DR
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Dankook University, Dongnam-gu, Choenan, Chungnam, Korea.
authors.forename: Myoung Jin
authors.initials: MJ
authors.lastname: Ho
authors.affiliation: College of Pharmacy, Dankook University, Dongnam-gu, Choenan, Chungnam, Korea.
authors.forename: Hyuck Jun
authors.initials: HJ
authors.lastname: Jung
authors.affiliation: College of Pharmacy, Dankook University, Dongnam-gu, Choenan, Chungnam, Korea.
authors.forename: Ha Ra
authors.initials: HR
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Dankook University, Dongnam-gu, Choenan, Chungnam, Korea.
authors.forename: Jun Seo
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Medical Laser, Graduate School, Dankook University, Dongnam-gu, Choenan, Chungnam, Korea.
authors.forename: Suk-Hyun
authors.initials: SH
authors.lastname: Yoon
authors.affiliation: College of Pharmacy, Dankook University, Dongnam-gu, Choenan, Chungnam, Korea.
authors.forename: Yong Seok
authors.initials: YS
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Chung-Ang University, Dongjak-gu, Seoul, Korea.
authors.forename: Young Wook
authors.initials: YW
authors.lastname: Choi
authors.affiliation: Department of Medical Laser, Graduate School, Dankook University, Dongnam-gu, Choenan, Chungnam, Korea; Department of Oral Physiology, College of Dentistry, Dankook University, Chungnam, Korea; Abel Medi-Tech Inc., Dongnam-gu, Cheonan, Chungnam, Korea.
authors.forename: Chung-Hun
authors.initials: CH
authors.lastname: Oh
authors.affiliation: College of Pharmacy, Dankook University, Dongnam-gu, Choenan, Chungnam, Korea.
authors.forename: Myung Joo
authors.initials: MJ
authors.lastname: Kang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004075:Diglycerides / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions / Q000737:chemistry; D005026:Ethylene Glycols / Q000737:chemistry; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D008297:Male; D050178:Monoglycerides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D016559:Tacrolimus / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: C000608598:Capmul MCM; D004075:Diglycerides; D004337:Drug Carriers; D004655:Emulsions; D005026:Ethylene Glycols; D050178:Monoglycerides; D011145:Polyvinyls; D013501:Surface-Active Agents; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D011092:Polyethylene Glycols; C000515:cremophor EL; C010111:carbitol; D005990:Glycerol; D016559:Tacrolimus
keywords: Soluplus; microemulsion; oral bioavailability; precipitation inhibitor; supersaturation; tacrolimus