title: Design and evaluation of a novel evodiamine-phospholipid complex for improved oral bioavailability.
abstract: A novel evodiamine (EVO)-phospholipid complex (EPLC) was designed to improve the bioavailability of EVO. A central composite design approach was employed for process optimization. EPLC were characterized by differential scanning calorimetry, ultraviolet spectroscopy, Fourier transformed infrared spectroscopy, (1)H-NMR spectroscopy, matrix-assisted laser desorption/ionization time-of-flight spectroscopy, apparent solubility, and dissolution rate. After oral administration of EPLC, the concentrations of EVO at different time points were determined by high-performance liquid chromatography. The optimal formulation for EPLC was obtained where the values of X                         (1), X                         (2), and X                         (3) were 2, 0.5, and 2.5 mg/mL, respectively. The average particle size and zeta potential of EPLC with the optimized formulation were 246.1 nm and -26.94 mV, respectively. The EVO and phospholipids in the EPLC were associated with non-covalent interactions. The solubility of EPLC in water and the dissolution rate of EPLC in phosphate-buffered solution (pH 6.8) were substantially enhanced. The plasma EVO concentration-time curves of EPLC and free EVO were both in accordance with the two-compartment model. The peak concentration and AUC(0-∞) of EPLC were increased, and the relative bioavailability was significantly increased to 218.82 % compared with that of EVO.
authors.affiliation: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, People's Republic of China.
authors.forename: Qunyou
authors.initials: Q
authors.lastname: Tan
authors.forename: Shan
authors.initials: S
authors.lastname: Liu
authors.forename: Xueliang
authors.initials: X
authors.lastname: Chen
authors.forename: Mingjun
authors.initials: M
authors.lastname: Wu
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Huafeng
authors.initials: H
authors.lastname: Yin
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.forename: Huarong
authors.initials: H
authors.lastname: Xiong
authors.forename: Jingqing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D026121:Indole Alkaloids / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D008956:Models, Chemical; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D004337:Drug Carriers; D004365:Drugs, Chinese Herbal; D026121:Indole Alkaloids; D010743:Phospholipids; C539353:evodamine