[Screening of Panax notoginsenoside water in oil microemulsion formulations and their evaluation in vitro and in vivo].
Water in oil (W/O) microemulsion formulation was developed to enhance intestinal absorption of ginsenoside Rb1 (Rb1) of panax notoginseng (PNS). Effects of W/O microemulsions on pharmacokinetics after intraduodenal administration, membrane fluidity and membrane transport of Rb, were studied in rats, liposomes and parallel artificial membrane permeability assay (PAMPA), respectively. Soybean phospholipids/ethanol (SP/EtOH) was selected as surfactant/cosurfactant, together with PNS 400 mg x mL(-1) solution and various kinds of oils, to prepare 11 W/O microemulsions. Most of the microemulsions can enhance Rb1 intestinal absorption significantly. Besides surfactant/cosurfactant, oil also had an effect on the enhanced absorption and the order of enhancement was as follows: glyceryl laurate approximately = isopropyl myristate > isopropyl palmitate > 2-ethylhexanol palmitate. The effection of absorption enhancement by the long chain glyceride ( > C14) is lower than that by the medium chain glyceride (C8 - C14). Most of W/O microemulsions were found to enhance the membrane fluidity of liposomes to different extents. In PAMPA analysis, efficient permeability coefficient (Pe) of diluted-microemulsion (D-ME) is mostly higher than that of PNS solution, which indicated the components of microemulision can facilitate the membrane permeability of the drug. Meanwhile, linearity correlation between Pe and ratio of relative bioavailability (Fr) was acquired for undiluted microemulison (ME). Therefore, W/O microemulsions can enhance intestinal absorption of Rbr, and this effect may be attiributed to its enhancement on membrane fluidity to a certain degree. PAMPA analysis could be brought into not only the investigation of membrane transport of crude drug, but also conditioned preformulation research (e.g. absorption enhancer etc.).
Han
Min
M
School of Pharmacy, Zhejiang University, Hangzhou 310058, China.
Fu
Shao
S
Fang
Xiao-ling
XL
D000818:Animals; D016503:Drug Delivery Systems; D004655:Emulsions; D036145:Ginsenosides / Q000008:administration & dosage* / Q000302:isolation & purification / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D008560:Membrane Fluidity; D009821:Oils; D053723:Panax notoginseng / Q000737:chemistry; D010539:Permeability; D010946:Plants, Medicinal / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013501:Surface-Active Agents / Q000737:chemistry; D014867:Water
D004655:Emulsions; D036145:Ginsenosides; D009821:Oils; D013501:Surface-Active Agents; D014867:Water; C104509:gelucire 44-14; D011092:Polyethylene Glycols; C442759:ginsenoside Rb1