title: Preparation Procedure and Pharmacokinetic Study of Water-in-Oil Nanoemulsion of Panax Notoginseng Saponins for Improving the Oral Bioavailability.
abstract: BACKGROUND
  Due to the effects of gastric acid, glycosidase and intestinal flora in the gastrointestinal environment, panax notoginseng saponins (PNS) can easily be resolved and metabolized when it is administered orally, limiting its oral bioavailability.
  
  
  METHODS
  The formula of PNS nanoemulsion (PNS-N) was optimized using a pseudoternary phase diagram, and the PNS-N was prepared by high pressure homogenization. The type, particle size, polydispersity index (PDI), refractive index, pH and content of PNS-N were characterized. In vitro characteristics were investigated by drug release and physical stability. The pharmacokinetic properties of PNS-N were studied with rat intestine and SD rats. The optimized nanoemulsion formulation was Labrafil M 1944CS (58%), SP/EtOH (Km=1) (25%), solution of PNS (400mg/ml) (17%).
  
  
  RESULTS
  The results showed that the average particle size was (28.17±0.39) nm with PDI of 0.116±0.032, refractive index of 1.4491±0.0009 and pH of 4.58±0.03. In addition, the contents of R1, Rg1 and Rb1 were (4.64±0.21) mg/mL, (19.16±0.27) mg/mL and (11.77±0.08) mg/mL, respectively. The optimized PNS-N formulation exhibited a sustained drug release with good stability. PNS-N is still clear and transparent, without layering and precipitation after six months. In the study of absorption kinetics of PNS-N in rat intestine, the Papp of three main components of PNS-N increased 5 times than PNS solution (PNS-SOL) in rat intestine. And pharmacokinetic study in SD rats suggested a 2.58-fold increase of oral bioavailability compared with PNS-SOL.
  
  
  CONCLUSIONS
  The PNS-N has increased the absolute availability of PNS obviously and nanoemulsion is a potential formulation to improve oral bioavailability for PNS.
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, No. 88 Yuquan Road, Nankai District, Tianjin 300193, P.R. China. lonerliuzd@163.com.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Lingling
authors.initials: L
authors.lastname: Ding
authors.forename: Chunhua
authors.initials: C
authors.lastname: Li
authors.forename: Zhongpeng
authors.initials: Z
authors.lastname: Yin
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Yan
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Pi
authors.forename: Jiawei
authors.initials: J
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Dongli
authors.initials: D
authors.lastname: Qi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004655:Emulsions; D008297:Male; D036103:Nanotechnology; D009821:Oils; D053723:Panax notoginseng / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000493:pharmacokinetics*; D014867:Water
chemical_list: D004655:Emulsions; D009821:Oils; D012503:Saponins; D014867:Water