Process optimization, characterization and pharmacokinetic evaluation in rats of ursodeoxycholic acid-phospholipid complex.
The purpose of this research was to study whether the bioavailability of ursodeoxycholic acid could be improved by administering ursodeoxycholic acid-phospholipid complex (UDCA-PLC) orally to rats. A central composite design approach was used for process optimization in order to obtain the acceptable UDCA-PLC. The physicochemical properties of the complex obtained by optimal parameters were investigated by means of scanning electron microscopy and X-ray diffraction. The pharmacokinetic parameters and bioavailability studies were conducted in rats of UDCA after oral administration of UDCA-PLC and UDCA tablet. Multiple linear regression analysis for process optimization revealed that the acceptable UDCA-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 XRD studies of UDCA-PLC obtained by the optimal parameters demonstrated that UDCA and phospholipids in the UDCA-PLC were combined by non-covalent bonds, not form new compounds. But pharmacokinetic parameters of the complex in rats were T(max) 1.6 h, C(max) 0.1346 microg/ml, AUC(0-infinity) 11.437 microg x h/ml, respectively. The relative bioavailability of UDCA of UDCA-PLC was increased by 241%,compared with the reference ursodeoxycholic acid tablet.
Yue
Peng-Fei
PF
302 Hospital of PLA&PLA Institute of Chinese Materia Medica, Beijing 100039, China.
Zhang
Wen-Jin
WJ
Yuan
Hai-Long
HL
Yang
Ming
M
Zhu
Wei-Feng
WF
Cai
Pei-Lie
PL
Xiao
Xiao-He
XH
D000818:Animals; D001682:Biological Availability; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008297:Male; D009928:Organ Specificity; D010743:Phospholipids / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*
D004337:Drug Carriers; D010743:Phospholipids; D014580:Ursodeoxycholic Acid