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

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In this paper we present a method for the synthesis of small particles of poorly water soluble drug substances using emulsions. In the first place, the drug is dissolved in an organic solvent and a water soluble surfactant is dissolved in water. Secondly, these two solutions are mixed to form an emulsion, where the organic solution is emulsified into small droplets in the aqueous phase. The action of the surfactant is partly to decrease the interfacial tension between the water and the organic solution, thus increasing the ease of emulsification, and partly to stabilize the droplets formed against aggregation, or coalescence. The final step in the process is to remove the organic solvent by evaporation in doing which the drug precipitates and one particle is formed in each droplet. If the surfactant is sufficiently effective in stabilizing the particles formed against coagula--tion, we have a suspension of small spherical drug particles. In this paper we use a model system consisting of cholesteryl acetate and toluene. Particles down to 50 nm were obtained by this method. The sizes of the particles were found to be dependent on the surfactant concentration and the emulsification energy.

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