Process optimization, characterization and evaluation in vivo of oxymatrine-phospholipid complex

作者：Yue, Peng-Fei^*; Yuan, Hai-Long; Li, Xian-Yi; Yang, Ming; Zhu, Wei-Feng

来源：International Journal of Pharmaceutics, 2010, 387(1-2): 139-146.

DOI：10.1016/j.ijpharm.2009.12.008

• Oxymatrine
• Phospholipid complex
• Optimization
• Physicochemical properties
• Pharmacokinetics

The objective of this study was to prepare oxymatrine-phospholipid complex (OMT-PLC) to enhance oral bioavailability of oxymatrine. A central composite design approach was used for process optimization. The physicochemical properties of the complex obtained by optimal parameters were investigated by means of differential scanning calorimetry (DSC), X-ray diffraction (XRD) and N-octanol/water partition coefficient. Compared with those of the physical mixture or oxymatrine, the hepatocytes permeability of oxymatrine-phospholipid complexes was studied. The concentrations of oxymatrine after oral administration of OMT-PLC at different time in rats were determined by HPCE. Multiple linear regression analysis for process optimization revealed that the acceptable OMT-PLC was obtained wherein the optimal values of X-1, X-2 and X-3 were 3, 60 degrees C and 3 h, respectively. The oxymatrine and phospholipids in the OMT-PLC were combined by non-covalent bond, not forming a new compound. The better hepatocytes permeability was obtained by the OMT-PLC. Pharmacokinetic parameters of the complex in rats were T-max 2.17 h, C-max 0.437 mu g ml(-1), AUC(0-infinity) 9.43 mu g h ml(-1), respectively. The bioavailability of oxymatrine in rats was increased remarkably after oral administration of OMT-PLC (p < 0.05), compared with those of oxymatrine or the physical mixture. This was mainly due to an improvement of the solubility of OMT-PLC.

• 出版日期2010-3-15
• 单位中国人民解放军第三０二医院; 江西中医药大学