title: A new strategy for enhancing the oral bioavailability of drugs with poor water-solubility and low liposolubility based on phospholipid complex and supersaturated SEDDS.
abstract: A novel supersaturated self-emulsifying drug delivery system (Super-SEDDS) loaded with scutellarin-phospholipid complex (SPC) was developed. The system aimed to address the limitations presented by conventional SEDDS as delivery carriers for drugs with poor water-solubility, low liposolubility and high dose. As an intermediate, SPC was first prepared based on the response surface design. The presence of amorphous scutellarin was demonstrated through differential scanning calorimetry (DSC) and X-ray diffraction (XRD), while enhanced liposolubility was confirmed through comparison with scutellarin powder via an octanol/water distribution test. On the basis of the solubility study and ternary phase diagram, Super-SEDDS containing SPC of up to 200% equilibrium solubility (Seq) was designed, which composed of ethyl oleate, Cremophor RH40 and Transcutol HP with a ratio of 60:25:15 (w/w%). The subsequent in vitro lipolysis study and ex vivo intestinal absorption test indicated that Super-SEDDS enhanced the cumulative dissolution from 70% to 100% and improved the intestinal absorption from 0.04 to 0.12 µg/cm(2) compared with scutellarin powder. Furthermore, an in vivo study demonstrated that Super-SEDDS achieved the AUC0-t of scutellarin up to approximate 1.7-fold as scutellarin powder. It was also proved superior to SPC and the conventional SEDDS. Super-SEDDS showed great potential for expanding the usage of SEDDS and could act as an alternative to conventional SEDDS.
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jiangling
authors.initials: J
authors.lastname: Wan
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau.
authors.forename: Tao
authors.initials: T
authors.lastname: Yi
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Huibi
authors.initials: H
authors.lastname: Xu
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yang
mesh_terms: D000284:Administration, Oral; D047310:Apigenin / Q000737:chemistry*; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D016503:Drug Delivery Systems / Q000379:methods*; D045703:Emulsifying Agents / Q000737:chemistry*; D005026:Ethylene Glycols; D005965:Glucuronates / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D011092:Polyethylene Glycols; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D045703:Emulsifying Agents; D005026:Ethylene Glycols; D005965:Glucuronates; D004364:Pharmaceutical Preparations; D010743:Phospholipids; C484876:scutellarin; C022131:cremophor; D011092:Polyethylene Glycols; D047310:Apigenin; C010111:carbitol