A method for the preparation of submicron particles of sparingly water-soluble drugs by precipitation in oil-in-water emulsions. I: Influence of emulsification and surfactant concentration.

A method for the synthesis of small particles of poorly water-soluble drug substances with emulsions is presented. The drug is dissolved in an organic solvent and a water-soluble surfactant is dissolved in water. These two solutions are mixed to form an emulsion in which the organic solution is emulsified into small droplets in the aqueous phase. The surfactant decreases the interfacial tension between the water and the organic solution, and thus increases the ease of emulsification, and stabilizes the droplets formed against aggregation or coalescence. The final step includes removal of the organic solvent by evaporation. The drug precipitates and one particle is formed from each droplet. If the surfactant is sufficiently effective in stabilizing the particles formed against coagulation, a suspension of small spherical drug particles is formed. A model system consisting of cholesteryl acetate and toluene is described. Particles with a diameter as low as 50 nm were obtained. The particle size was dependent on the surfactant concentration and on the emulsification energy.