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 phospholipi d-based microemulsion system. Microemulsions composed of ethyl oleate. leci thin and distearoylphosphatidyl-ethanolamine-N-poly(ethyleneglycol) 2000 (D SPE-PEG) were prepared using ethanol as a cosolvent. The effect of formulat ion variables on the particle size of the microemulsion was investigated. F lurbiprofen concentrations in plasma and various organs after the intraveno us administration of flurbiprofen-loaded microemulsion were measured and co mpared with those after the intravenous administration of flurbiprofen axet il-entrapped oemulsion (Lipfen(R), 50 mg/5 ml as flurbiprofen axetil) and f lurbiprofen solution. Phospholipid-based microemulsions could solubilize mo re than 10 mg ml(-1) of flurbiprofen at the ratio of vehicle to drug at lea st 10:1, if the oil contents (10 or 20%) of common parenteral emulsions wer e used. The half-life, AUC and MRT of flurbiprofen loaded in microemulsion (ethyl oleate:lecithin:DSPE-PEG:flurbiprofen = 8:3:1:1.2) increased signifi cantly. The biodistribution of flurbiprofen loaded in this microemulsion wa s quite different from others. Reticuloendothelial uptake of flurbiprofen l oaded in microemulsion decreased compared with that in solution or Lipfen(R ). It is concluded that the current microemulsion system might be applicabl e to formulate the parenteral dosage form of poorly water-soluble flurbipro fen without chemical modification. (C) 1999 Elsevier Science B.V. All right s reserved.