title: A silica-supported solid dispersion of bifendate using supercritical carbon dioxide method with enhanced dissolution rate and oral bioavailability.
abstract: In this study, to enhance the dissolution rate and oral bioavailability of bifendate, a silica-supported solid dispersion (SD) of bifendate was prepared using supercritical carbon dioxide (ScCO2) technology. The properties of bifendate-silica SD were characterized by differential scanning calorimetry (DSC), X-ray diffraction (X-RD) and scanning electron microscopy. The pharmacokinetic study was carried out in beagle dogs using commercial bifendate dropping pills as a reference which is a conventional SD formulation of bifendate and PEG6000. A novel method of Ultra Performance Convergence Chromatography-tandem mass spectrometry (UPC(2)™-MS/MS) method was applied to determine bifendate concentration in plasma. The amorphous state of bifendate in bifendate-silica SD was revealed in X-RD and DSC when the ratios of bifendate and silica were 1:15 and 1:19, respectively. In vitro dissolution rate was significantly improved with cumulative release of 67% within 20 min relative to 8% for the physical mixture of bifendate and silica, and which was also higher than the commercial dropping pill of 52%. After storage at 75% relative humidity (RH) for 10 d, no recrystallization was found and reduced dissolution rate was obtained due to the absorption of moisture. In pharmacokinetic study, Cmax and AUC0-t for bifendate-silica SD were 153.1 ng/ml and 979.8 ng h/ml, respectively. AUC0-t of bifendate-silica SDs was ∼1.6-fold higher than that of the commercial dropping pills. These results suggest that adsorbing bifendate onto porous silica via ScCO2 technique could be a feasible method to enhance oral bioavailability together with a higher dissolution rate.
authors.affiliation: a Department of Pharmaceutics and.
authors.forename: Cuifang
authors.initials: C
authors.lastname: Cai
authors.affiliation: b Department of Pharmaceutical Analysis , Shenyang Pharmaceutical University , Shenyang , PR China.
authors.forename: Muhua
authors.initials: M
authors.lastname: Liu
authors.affiliation: b Department of Pharmaceutical Analysis , Shenyang Pharmaceutical University , Shenyang , PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: b Department of Pharmaceutical Analysis , Shenyang Pharmaceutical University , Shenyang , PR China.
authors.forename: Bei
authors.initials: B
authors.lastname: Guo
authors.affiliation: b Department of Pharmaceutical Analysis , Shenyang Pharmaceutical University , Shenyang , PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chang
authors.affiliation: b Department of Pharmaceutical Analysis , Shenyang Pharmaceutical University , Shenyang , PR China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: b Department of Pharmaceutical Analysis , Shenyang Pharmaceutical University , Shenyang , PR China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Yang
authors.affiliation: b Department of Pharmaceutical Analysis , Shenyang Pharmaceutical University , Shenyang , PR China.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D002245:Carbon Dioxide / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D004285:Dogs; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D012995:Solubility
chemical_list: D001713:Biphenyl Compounds; C465548:bifendate; D002245:Carbon Dioxide; D012822:Silicon Dioxide
keywords: Bifendate; bioavailability; dissolution; silica; supercritical carbon dioxide