The effect of a lipophilic drug, felodipine, on the formation of nanoemulsions upon phase inversion induced by temperature variation

Abstract

The correlation between a dispersed phase/dispersion medium interfacial tension σ at a storage temperature of 22°C and the dispersity and stability of oil-in-water miniemulsions, which result from temperature-induced phase inversion, has been revealed for hydrocarbon/polyoxyethylene(4)lauryl ether/water systems (in the presence and absence of felodipine) with the help of conductometry, tensiometry, and dispersion analysis. At σ < 3.5 × 10^–6 N/m, oil-in-water nanoemulsions, which have narrow monomodal particle size distributions and are stable for a month, are a fortiori formed. Felodipine has been shown to serve as a cosurfactant, which is incorporated into the adsorption layer of a basic stabilizing nonionic surfactant. Therewith, σ values increase and the temperature of phase inversion decreases, while the concentration of the basic surfactant in an optimal composition must be substantially reduced. A heptane/water nanoemulsion (droplet size of 75 nm) stabilized with a basic nonionic surfactant and Tween 80 exhibits a high solubilization capacity with respect to felodipine and ensures its efficient mass transfer through a model membrane.