title: Role of a novel pyridostigmine bromide-phospholipid nanocomplex in improving oral bioavailability.
abstract: A novel pyridostigmine bromide (PB)-phospholipid nanocomplex (PBPLC) was prepared to increase the bioavailability of PB. A central composite design approach was employed for process optimization. The physicochemical properties of PBPLC were investigated by means of differential scanning calorimetry, ultraviolet spectroscopy, Fourier transformed infrared spectroscopy and the n-octano/water partition coefficient. The intestinal permeability of PBPLC was observed via a single pass intestinal perfusion in rats. After oral administration of PBPLC, the concentrations of PB at predetermined time points were determined by HPLC, and the pharmacokinetic parameters were computed by DAS 2.1.1 software. Multiple linear regression analysis for process optimization revealed that the optimal PBPLC was obtained when the values of X(1), X(2), and X(3) were 8, 40°C, and 4 mg/mL, respectively. The average particle size and zeta potential of PBPLC with the optimized formulation were 204.60 nm and -25.12 mV, respectively. Non-covalent interactions between PB and phospholipids were found in the PBPLC. The n-octanol/water partition coefficient of PBPLC was substantially increased. PBPLC had better intestinal permeability in comparison with free PB. Mean plasma drug concentration-time curves of PBPLC and free PB after oral administration were both in accordance with the two-compartment open model. The values of pharmacokinetic parameters of PBPLC and free PB were the peak time (T(max)) 2 h vs 2 h, the maximum concentration (C(max)) 22.79 μg/mL vs 6.00 μg/mL, and the value of the area under the concentration vs time curve (AUC(0-∞)) 7128.21 μg·min/mL vs 1772.36 μg·min/mL, respectively. In conclusion, compared with free PB, PBPLC remarkably improves the oral bioavailability of PB, which is likely due to its higher lipophilicity and permeability.
authors.affiliation: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Qun-you
authors.initials: QY
authors.lastname: Tan
authors.forename: Ni-ni
authors.initials: NN
authors.lastname: Hu
authors.forename: Guo-dong
authors.initials: GD
authors.lastname: Liu
authors.forename: Hua-feng
authors.initials: HF
authors.lastname: Yin
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Lu-yang
authors.initials: LY
authors.lastname: Lu
authors.forename: Jing-qing
authors.initials: JQ
authors.lastname: Zhang
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004339:Drug Compounding; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D016014:Linear Models; D008297:Male; D008954:Models, Biological; D053758:Nanoparticles; D036103:Nanotechnology; D010539:Permeability; D010743:Phospholipids / Q000737:chemistry*; D011729:Pyridostigmine Bromide / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry
chemical_list: D002800:Cholinesterase Inhibitors; D010743:Phospholipids; D012997:Solvents; D014867:Water; D011729:Pyridostigmine Bromide; D020003:1-Octanol