Water in oil microemulsions containing NaCl for transdermal delivery of fluorouracil

This study is to prepare the W/O microemulsion containing NaCl and fluorouracil (5-Fu) as a model drug to investigate the transdermal characteristics and skin irritation of the microemulsion in vitro.  Isopropylmyristate (IPM) acting as oil phase, Aerosol-OT (AOT) as surfactant, Tween 85 as cosurfactant, NaCl solution was added dropwise to the oil phase to prepare W/O microemulsion at room temperature using magnetic stirring, and then 5-Fu powder was added.  According to the area of microemulsion based on the pseudo-tertiary phase diagrams, the optimum formulation was screened initially.  And the permeation flux of fluorouracil across excised mice skin was determined in vitro using Franz diffusion cells to study the influence of the amount of water and the drug loading capacity and optimize the formulation further.  Refer to 5-Fu cream, the irritation of microemulsion on the rat skin was studied.  The optimum formulation was composed of 0.7% (w/v) 5-Fu, 50% NaCl solution (0.05 mol·L⁻¹), 20% mix-surfactant (AOT/Tween 85, K_m = 2) and 29.3% oil (IPM).  The cumulative amount of fluorouracil permeated in 12 h was (2 013.4 ± 41.6) µg·cm⁻², 20.23 folds and 10.38 folds more than 0.7% fluorouracil aqueous solution and 2.5% (w/w) fluorouracil cream, respectively.  Microemulsion exhibited some irritation, but could be reversed after drug withdrawal.  The addition of NaCl significantly increased the content of water and the drug loading in microemulsion systems.  The NaCl/AOT-Tween 85/IPM microemulsion system promoted the permeation of fluorouracil greatly, which may be a promising vehicle for the transdermal delivery of fluorouracil and other hydrophilic drug.