Preparation, characterization, and bioavailability of ursodeoxycholic acid-phospholipid complex in vivo.
The aim of this study was to prepare ursodeoxycholic acid-phospholipid complex (UDCA-PLC) to enhance oral bioavailability of UDCA, and the physicochemical properties of the complex were studied. Compared with those of UDCA tablet after oral administration in rats, the main pharmacokinetic characteristics and bioavailability of UDCA-PLC orally administered were evaluated. Tetrahydrofuran was used as a reaction medium, UDCA and phospholipids were resolved into the medium, and UDCA-PLC was formed after the organic solvent was evaporated off under vacuum condition. The physicochemical properties of the complex were evaluated using scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction, particle size distribution analysis, and n-octanol/water partition coefficient (P) study. The blood concentrations of UDCA-PLC and UDCA tablet at different time points after oral administration in rats were assayed by high-performance liquid chromatography (HPLC) after derivatization. The pharmacokinetic parameters were computed by software program 3p87. The X-ray diffraction and DSC studies showed that UDCA and phospholipids in the UDCA-PLC were combined by noncovalent bond, not forming a new compound, and n-octanol/water partition coefficient (P) of UDCA-PLC was effectively enhanced. The mean serum concentration-time curves of UDCA after oral administration of UDCA-PLC and UDCA tablet in rats were both in accordance with open two-compartment model. Pharmacokinetic parameters of UDCA tablet and the PLC in rats were T(max) 1.9144 and 1.5610 h, C(max) 0.0576 and 0.1346 microg/mL, and AUC(0-infinity) 4.736 and 11.437 microg h/mL, respectively. The bioavailability of UDCA in rats was significantly different (p < .05) compared with those of UDCA tablet after administration. The UDCA-PLC would be more prospective formulation in future.
Yue
Peng-Fei
PF
302 Hospital of PLA&PLA Institute of Chinese Materia Medica, Beijing.
Yuan
Hai-Long
HL
Xie
Huan
H
Xiao
Xiao-He
XH
Yang
Ming
M
Liao
Mei-Xiang
MX
Zhu
Wei-Feng
WF
Cai
Pei-Lie
PL
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002756:Cholagogues and Choleretics / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry*; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013607:Tablets; D014580:Ursodeoxycholic Acid / Q000493:pharmacokinetics*; D014961:X-Ray Diffraction
D002756:Cholagogues and Choleretics; D004337:Drug Carriers; D010743:Phospholipids; D013607:Tablets; D014580:Ursodeoxycholic Acid