title: Preparation and pharmaceutical evaluation of new tacrolimus-loaded solid self-emulsifying drug delivery system.
abstract: The purpose of this study was to develop a novel tacrolimus-loaded solid self-emulsifying drug delivery system (SEDDS) using Labrafac as an oil phase. The ternary phase diagram was plotted with Labrafac, Labrasol and Lauroglycol used as an oil, surfactant and co-surfactant, respectively. The liquid SEDDS formulated with Labrasol, Lauroglycol and Labrafac (70:15:15, volume ratio) furnished the smallest emulsion globule size. The solid SEDDS was obtained by spray-drying the liquid mixture containing the liquid SEDDS with 5 % tacrolimus and silicon dioxide. Furthermore, dissolution of tacrolimus from the solid SEDDS and pharmacokinetics in rats was studied compared to the commercial product. The solid SEDDS produced relatively larger emulsion globule size than that exhibited by the corresponding liquid SEDDS. However, this size variation was not significantly different. The solid SEDDS with approximately 280 nm emulsion droplet size improved the dissolution of the drug compared to drug power and the commercial product. It resulted in significantly higher plasma concentration, AUC and Cmax, and shorter Tmax values than did the commercial product (p < 0.05). The enormously enhanced oral bioavailability of tacrolimus in rats was attributed to relatively faster absorption due to accelerated dissolution of the drug from the solid SEDDS. Therefore, this novel solid SEDDS prepared with Labrafac as an oil phase is an excellent way to achieve better bioavailability of tacrolimus given via the oral route.
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan, 712-749, South Korea.
authors.forename: Youn Gee
authors.initials: YG
authors.lastname: Seo
authors.forename: Dong-Wuk
authors.initials: DW
authors.lastname: Kim
authors.forename: Kwan Hyung
authors.initials: KH
authors.lastname: Cho
authors.forename: Abid Mehmood
authors.initials: AM
authors.lastname: Yousaf
authors.forename: Dong Shik
authors.initials: DS
authors.lastname: Kim
authors.forename: Jeong Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions; D005989:Glycerides / Q000737:chemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007848:Laurates / Q000737:chemistry; D008297:Male; D011409:Propylene Glycols / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D012995:Solubility; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014280:Triglycerides / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D005989:Glycerides; D007166:Immunosuppressive Agents; D007848:Laurates; D011409:Propylene Glycols; D014280:Triglycerides; C542236:labrafac WL 1349; C440220:Labrasol; C098387:propyleneglycol monolaurate; D016559:Tacrolimus