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

摘要

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 microg ml(-1), AUC(0-infinity) 9.43 microg 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.