title: Process optimization, characterization and pharmacokinetic evaluation in rats of ursodeoxycholic acid-phospholipid complex.
abstract: 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.
authors.affiliation: 302 Hospital of PLA&PLA Institute of Chinese Materia Medica, Beijing 100039, China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Yue
authors.forename: Wen-Jin
authors.initials: WJ
authors.lastname: Zhang
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Yuan
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Zhu
authors.forename: Pei-Lie
authors.initials: PL
authors.lastname: Cai
authors.forename: Xiao-He
authors.initials: XH
authors.lastname: Xiao
mesh_terms: 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*
chemical_list: D004337:Drug Carriers; D010743:Phospholipids; D014580:Ursodeoxycholic Acid