Preparation, characterization and in vivo evaluation of bergenin-phospholipid complex  

作　　者：Xuan QIN Yang YANG Ting-ting FAN Tao GONG Xiao-ning ZHANG Yuan HUANG 

机构地区：[1]Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China [2]School of Medicine, Tsinghua University, Beijing 100084, China

出　　处：《Acta Pharmacologica Sinica》2010年第1期127-136,共10页中国药理学报（英文版）

摘　　要：Aim： To prepare a bergenin-phospholipid complex （BPC） to increase oral bioavailability of the drug. Methods： In order to obtain the acceptable BPC, a spherical symmetric design-response surface methodology was used for process optimization. The influence of reaction medium, temperature, drug concentration and drug-to-phospholipid ratio on the combination percentage and content of bergenin in BPC were evaluated. BPC was then characterized by thin-layer chromatography （TLC）, high-performance liquid chromatography （HPLC）, ultra-violet （UV） spectroscopy, fourier transform infrared spectroscopy （FT-IR）, differential scanning calorimetry （DSC） and X-ray powder diffraction. The physicochemical properties such as microscopic shape, particle size, zetapotential, solubility, crystalline form, and hygroscopicity were tested. The pharmacokinetic characteristics and bioavailability of BPC were investigated after oral administration in rats in comparison to bergenin and the physical mixture （bergenin and phospholipids）. Results： BPC was successfully prepared under the optimum conditions [temperature=60 ℃, drug concentration=80 g/L and drug-tophospholipids ratio=0.9 （w/w）]. The combination percentage was 100.00%±0.20%, and the content of bergenin in the complex was 45.98%±1.12%. Scanning electron microscopy and transmission electron microscopy of BPC showed spherical particles. The average particle size was 169.2±20.11 nm and the zeta-potential was -21.6±2.4 mV. The solubility of BPC in water and in n-octanol was effectively enhanced. The Cmax and AUC0→∞ of BPC were increased, and the relative bioavailability was significantly increased to 439% of bergenin. Conclusion： The BPC is a valuable delivery system to enhance the oral absorption of bergenin.Aim： To prepare a bergenin-phospholipid complex （BPC） to increase oral bioavailability of the drug. Methods： In order to obtain the acceptable BPC, a spherical symmetric design-response surface methodology was used for process optimization. The influence of reaction medium, temperature, drug concentration and drug-to-phospholipid ratio on the combination percentage and content of bergenin in BPC were evaluated. BPC was then characterized by thin-layer chromatography （TLC）, high-performance liquid chromatography （HPLC）, ultra-violet （UV） spectroscopy, fourier transform infrared spectroscopy （FT-IR）, differential scanning calorimetry （DSC） and X-ray powder diffraction. The physicochemical properties such as microscopic shape, particle size, zetapotential, solubility, crystalline form, and hygroscopicity were tested. The pharmacokinetic characteristics and bioavailability of BPC were investigated after oral administration in rats in comparison to bergenin and the physical mixture （bergenin and phospholipids）. Results： BPC was successfully prepared under the optimum conditions [temperature=60 ℃, drug concentration=80 g/L and drug-tophospholipids ratio=0.9 （w/w）]. The combination percentage was 100.00%±0.20%, and the content of bergenin in the complex was 45.98%±1.12%. Scanning electron microscopy and transmission electron microscopy of BPC showed spherical particles. The average particle size was 169.2±20.11 nm and the zeta-potential was -21.6±2.4 mV. The solubility of BPC in water and in n-octanol was effectively enhanced. The Cmax and AUC0→∞ of BPC were increased, and the relative bioavailability was significantly increased to 439% of bergenin. Conclusion： The BPC is a valuable delivery system to enhance the oral absorption of bergenin.

关 键 词：BERGENIN phospholipid complex spherical symmetric design-response surface methodology physicochemical properties BIOAVAILABILITY 

分 类 号：TQ460.72[医药卫生—药物分析学] X503.225[化学工程—制药化工]