Phospholipid-based microemulsions of flurbiprofen by the spontaneous emulsification process.
The purpose of this study was to investigate the possibility for parenteral delivery of flurbiprofen without chemical modification using a phospholipid-based microemulsion system. Microemulsions composed of ethyl oleate, lecithin and distearoylphosphatidyl-ethanolamine-N-poly(ethyleneglycol) 2000 (DSPE-PEG) were prepared using ethanol as a cosolvent. The effect of formulation variables on the particle size of the microemulsion was investigated. Flurbiprofen concentrations in plasma and various organs after the intravenous administration of flurbiprofen-loaded microemulsion were measured and compared with those after the intravenous administration of flurbiprofen axetil-entrapped emulsion (Lipfen(R), 50 mg/5 ml as flurbiprofen axetil) and flurbiprofen solution. Phospholipid-based microemulsions could solubilize more than 10 mg ml-1 of flurbiprofen at the ratio of vehicle to drug at least 10:1, if the oil contents (10 or 20%) of common parenteral emulsions were used. The half-life, AUC and MRT of flurbiprofen loaded in microemulsion (ethyl oleate:lecithin:DSPE-PEG:flurbiprofen=8:3:1:1.2) increased significantly. The biodistribution of flurbiprofen loaded in this microemulsion was quite different from others. Reticuloendothelial uptake of flurbiprofen loaded in microemulsion decreased compared with that in solution or Lipfen(R). It is concluded that the current microemulsion system might be applicable to formulate the parenteral dosage form of poorly water-soluble flurbiprofen without chemical modification.
Park
K M
KM
College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Ku, Seoul 151-742, South Korea.
Lee
M K
MK
Hwang
K J
KJ
Kim
C K
CK
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D004655:Emulsions; D000431:Ethanol / Q000737:chemistry; D005480:Flurbiprofen / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008081:Liposomes; D008863:Microspheres; D009829:Oleic Acids / Q000737:chemistry; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D014018:Tissue Distribution
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004655:Emulsions; D008081:Liposomes; D009829:Oleic Acids; D010713:Phosphatidylcholines; D010743:Phospholipids; D000431:Ethanol; D011092:Polyethylene Glycols; D005480:Flurbiprofen; C033180:ethyl oleate