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

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 X1, X2 and X3 were 3, 60 °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 Tmax 2.17 h, Cmax 0.437 μg ml−1, AUC0–∞ 9.43 μg 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.