Microemulsions of Potassium Oleate, Tween-20, Propylene Carbonate, and Ethylene Glycol as Drug Vehicles for Mefenamic Acid

Different microemulsions were prepared with and without mefenamic acid (MFA). The base microemulsion was mainly composed of distilled water; the aqueous phase, propylene carbonate; the oil phase, potassium oleate; the surfactant, and finally di-ethylene glycol; the cosurfactant. The effect of mixing ionic (potassium oleate) with nonionic (Tween-20) surfactant was investigated via constructing the phase diagrams of such systems. Changes in conductivity and viscosity of the freshly prepared microemulsion over time were monitored as an indication for the stability of the microemulsion. Measurements were carried out at room temperature, after a freeze-thaw cycle and also after storage for 3 days at 60°C, where the latter is treated as an accelerated test for the time-temperature effects on the stability of a microemulsion. It was found that a set of surfactants, instead of a single surfactant, and inclusion of cosurfactant resulted in a broader region where a stable microemulsion is predominant. At a mass ratio of 1:2 of potassium oleate to Tween-20, O/W microemulsions were found to have maximum stability among all examined systems, under the accelerated test, such that they have a minimum portion of combined surfactants and cosurfactant of 60 wt% and maximum of 80 wt%. With the aforementioned specifications, no phase separation and neither significant change in the conductivity nor in the viscosity was observed in any of the examined systems after subjecting them both to the accelerated and freeze-thaw cycle test, indicating that such systems were thermodynamically stable. Samples of micro emulsions passing previous tests were further subjected to an acidic medium by dispersing 1 g of MFA-containing microemulsion in 10 g HCl solution (pH 1) in a shaking water bath at 37°C, for a 6 hour period. The maximum solubility of MFA in a stable microemulsion was approximately 5 wt%, evaluated at room temperature.