Formation of colloidal dispersions of organic materials in aqueous media by solvent shifting

This paper describes the preparation of colloidal dispersions of water-insoluble organic materials by a solvent-shifting procedure, in which a concentrated solution of an organic solute in a water-miscible organic solvent is dispersed into a large volume of aqueous (nonsolvent) bulk solution containing colloidal stabilizers. In the majority of cases studied, the solute separates as 0.1-0.5 mum amorphous particles. The particle size is strongly correlated with the local supersaturation, i.e., the ratio of the solute feed concentration to the instantaneous value of the equilibrium solubility in the bulk, and also shows a weak dependence on the solute feed concentration. The results obtained on systematic variation of the precipitation conditions, including the amount of organic solvent in the aqueous phase, the solute feed concentration, and the mixing conditions, are discussed in terms of a mechanism of particle formation comprising dispersion of the feed solution as small droplets, followed by solvent/water counterdiffusion at the interface. Rapidly decreasing solvent quality, resulting from this interdiffusion, leads to local liquid-liquid phase separation by spinodal decomposition. This mechanism is shown to be consistent with the preferential formation of noncrystalline (amorphous) particles and with the observed changes in particle size and formation rate.