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 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.
Yue
Peng-Fei
PF
Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China. ypfpharm@126.com
Yuan
Hai-Long
HL
Li
Xian-Yi
XY
Yang
Ming
M
Zhu
Wei-Feng
WF
D000284:Administration, Oral; D000470:Alkaloids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D022781:Hepatocytes / Q000378:metabolism; D016014:Linear Models; D008297:Male; D010539:Permeability; D010743:Phospholipids / Q000737:chemistry*; D011807:Quinolizines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D012995:Solubility; D013997:Time Factors; D014961:X-Ray Diffraction; D000093842:Matrines
D000470:Alkaloids; D000998:Antiviral Agents; D004337:Drug Carriers; D010743:Phospholipids; D011807:Quinolizines; C037573:oxymatrine; D000093842:Matrines