title: Water-in-oil-in-water double emulsions: an excellent delivery system for improving the oral bioavailability of pidotimod in rats.
abstract: The aims of this study were to prepare fine pidotimod-containing water-in-oil-in-water (W/O/W) double emulsions and to investigate the possibility of those emulsions as a delivery system for promoting the oral bioavailability of pidotimod. A modified two-step emulsification procedure was applied to prepare the double emulsions using medium-chain triglyceride as the oil phase, Tween 80 as the hydrophilic emulsifier, and Span 80 alone or in combination with different amount of phospholipids as the lipophilic emulsifiers. A fine W/O/W emulsion, with the encapsulation efficiency of 82 ± 3.4%, mean oil-droplet diameter of 3.93 ± 0.25 μm, and viscosity of 36.4 ± 0.93 mPa · s at 25 °C and 300 s(-1), was stable for 1 month at 4 °C. In addition, the oral bioavailability of pidotimod in rats, after intragastric administration of W/O/W double emulsions, was significantly higher than that of pidotimod control solution. Moreover, the maximum uptake time was significantly prolonged, suggesting an extra absorption pathway for W/O/W emulsions: a lymphatic circulation pathway. Those results demonstrated that W/O/W emulsions could become a potential formulation for improving the oral bioavailability of poorly absorbable drugs and suggested an important technology platform for the oral administration of peptide and peptidomimetic drugs.
authors.affiliation: Pharmaceutical Research Institute, China Pharmaceutical University, Nanjing, China.
authors.forename: Xiaole
authors.initials: X
authors.lastname: Qi
authors.forename: Lishuang
authors.initials: L
authors.lastname: Wang
authors.forename: Jiabi
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D045703:Emulsifying Agents / Q000737:chemistry; D004655:Emulsions; D008297:Male; D010316:Particle Size; D057786:Peptidomimetics / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D053778:Thiazolidines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D014280:Triglycerides / Q000737:chemistry*; D014783:Viscosity; D014867:Water / Q000737:chemistry*
chemical_list: D045703:Emulsifying Agents; D004655:Emulsions; D057786:Peptidomimetics; D053778:Thiazolidines; D014280:Triglycerides; D014867:Water; C064893:pidotimod; D011761:Pyrrolidonecarboxylic Acid