Preparation and evaluation of flurbiprofen-loaded microemulsion for parenteral delivery.
The purpose of this study was to improve the solubility of flurbiprofen, a poorly water-soluble drug, in an oil-in-water (o/w) microemulsion that is suitable for parenteral administration. Microemulsions with varying ratios of oil to surfactant were prepared with ethyl oleate, Tween 20 and isotonic solution. The effect of formulation variables on the particle size of microemulsion and solubility of flurbiprofen in microemulsion system was investigated. The pharmacokinetic parameters of flurbiprofen after intravenous administration of flurbiprofen-loaded microemulsion were compared with those of a solution of the drug. The mean droplet diameter of microemulsion containing less than 1% (w/w) of flurbiprofen was below 100 nm. The maximum solubility of flurbiprofen in the microemulsion system was found to be 10 mg/ml. However, the mean droplet diameters of flurbiprofen-loaded o/w microemulsions tend to be increased at room temperature. The pharmacokinetic parameters of flurbiprofen after intravenous administration of flurbiprofen-loaded microemulsion to rats were not significantly different from those of flurbiprofen in phosphate-buffered saline solution. It can be concluded that microemulsions of flurbiprofen prepared with ethyl oleate and Tween 20 can be used as a parenteral drug carrier for this and other poorly water-soluble drugs, provided that physical stability can be properly addressed.
Park
K M
KM
College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Ku, Seoul, South Korea.
Kim
C K
CK
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004355:Drug Stability; D004655:Emulsions; D005079:Excipients / Q000737:chemistry; D005480:Flurbiprofen / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D009821:Oils / Q000737:chemistry; D009829:Oleic Acids / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D014867:Water / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004655:Emulsions; D005079:Excipients; D009821:Oils; D009829:Oleic Acids; D011136:Polysorbates; D013501:Surface-Active Agents; D014867:Water; D005480:Flurbiprofen; C033180:ethyl oleate