Studies On Flurbiprofen Microemulsion

Flurbiprofen microemulsion, choosing flurbiprofen as the model drug, was thermodynamically stable oil-in-water microemulsion. Flurbiprofen (FP), a new nonsteroidal anti-inflammatory and analgesic drug, has been mainly used for acute gout, osteoarthritis and acute pain. Most oral dosage forms of FP had low bioavailability because FP could hardly dissolve. Therefore, microemulsion (ME) was selected as the carrier to prepare FPME oral solution to increase dissolution, advance absorption and enhance bioavailability of FP.In the investigations of the pharmaceutical preformulation, the physico-chemical properties of FP were studied. The ionization constant and partition coefficient were determined as 5.42 and 21.10. The solubilities of FP in water, 0.1mol/L HC1 and pH6.8PBS in 37℃ were 41.12, 10.75 and 72.73μg/mL respectively. The release rate of FP in water fitted Hixson-Crowell model, and the release rate constant was 1.04h^-1. Two methods, UV spectrophotometry and the first-order derivative spectrophotometry, were developed for in vivtro assay. The first-order derivative spectrophotometry could eliminate the disturbance of excipients on analysis.Ethyl butyrate(EB), ethyl oleate (EO) and soybean oil (SBO) were used for oils. Labrasol, Tween80 and Tween 20 were selected as surfactants (Sf). Ethanol, 1,2-propanol and n-butanol were used for cosurfactants (CoSf). The pseudo-ternary phase diagrams were obtained with above oils, Sf , CoSf and water. The effects of oils,Sf,CoSf, the mass ratio of Sf and CoSf, pH and ionic strength of water, additives, temperature, dispersion methods and order of mixing on the phase diagrams were investigated. The optimum formulation and...