title: Enhancing in vitro dissolution and in vivo bioavailability of fenofibrate by solid self-emulsifying matrix combined with SBA-15 mesoporous silica.
abstract: Mesoporous silica Santa Barbara amorphous-15 (SBA-15), derived from supermolecular assemblies of surfactant Pluronic(®) P123 with well-ordered 2-D hexagonal pores, was investigated as a reservoir to construct a novel solid self-emulsifying matrix for enhancing the oral bioavailability of fenofibrate (FNB). The emulsification rate and droplet size of a liquid self-emulsifying delivery system (SEDDS) were analyzed for optimization. SBA-15 was then added to the ethanol solution containing liquid SEDDS, and the obtained suspension changed into solid SEDDS matrix via solvent evaporation. The characterizations by SEM and XRD revealed that the solid matrix consisted of particles with smooth surface and FNB was completely transformed into molecular or amorphous state in the formulation. When introduced to aqueous media under gentle agitation, the solid matrix exhibited excellent self-emulsification properties and formed a uniform microemulsion with mean diameter of 117.35 ± 2.33 nm. The solid SEDDS matrix showed faster in vitro release rate than the raw powder and commercial capsule. The absorption of FNB delivered by solid SEDDS matrix was significantly improved in beagle dogs, and its Cmax and AUC values were about 8- and 4-fold greater than those of commercial products, respectively. In conclusion, SBA-15 emerged as a promising reservoir for SEDDS to enhance the bioavailability of poorly water-soluble drugs, which may provide a new strategy for advanced therapies.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China; Research and Development Center of Pharmaceutical Engineering, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Guilan
authors.initials: G
authors.lastname: Quan
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Wu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Zhengwen
authors.initials: Z
authors.lastname: Zhan
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Chan
authors.initials: C
authors.lastname: Zhou
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Bao
authors.initials: B
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Zhengzan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Guangzhou Neworld Pharmaceutical Ltd., Co., Guangzhou 510006, PR China.
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China. Electronic address: pxin_1385@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Pan
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China; Research and Development Center of Pharmaceutical Engineering, Sun Yat-sen University, Guangzhou 510006, PR China. Electronic address: chuanbin_wu@126.com.
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D004285:Dogs; D065546:Drug Liberation; D045703:Emulsifying Agents / Q000737:chemistry*; D004655:Emulsions / Q000737:chemistry*; D011345:Fenofibrate / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008657:Metabolic Clearance Rate; D008855:Microscopy, Electron, Scanning; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D045703:Emulsifying Agents; D004655:Emulsions; D000960:Hypolipidemic Agents; C509969:SBA-15; D012822:Silicon Dioxide; D011345:Fenofibrate
keywords: Bioavailability; Fenofibrate; Mesoporous silica; Poorly water-soluble drug; Self-emulsifying drug delivery system