A silica-supported solid dispersion of bifendate using supercritical carbon dioxide method with enhanced dissolution rate and oral bioavailability. (3rd March 2016)

• Record Type: Journal Article
• Authors: Cai, Cuifang; Liu, Muhua; Li, Yun; Guo, Bei; Chang, Hui; Zhang, Xiangrong; Yang, Xiaoxu; Zhang, Tianhong
• Is Part Of: Drug development and industrial pharmacy. Volume 42:Number 3(2016:Mar.)
• Page Start: 412
• Page End: 417
• Publication Date: 2016-03-03
• Subjects: Bifendate -- bioavailability -- dissolution -- silica -- supercritical carbon dioxide; Pharmaceutical chemistry -- Periodicals; Pharmaceutical industry -- Periodicals; Drug Industry -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615.05
• DOI: 10.3109/03639045.2015.1071833
• Languages: English
• ISSNs: 0363-9045

Abstract

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, C max 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.