Preparation of solid particle dispersions by solvent shifting

Organic solid particle dispersions are useful for a number of industrial applications, including photography, pharmaceuticals, food, biotechnology and inks. This work describes precipitation by solvent shifting to prepare dispersions as an alternative to media milling, which is energy intensive and time consuming. In particular, we have studied the precipitation of an organic dye useful in photographic film.; In the solvent shifting technique, the dye is dissolved in a water-miscible organic solvent and added to an aqueous solution containing colloidal stabilizers. Under suitable conditions of composition and mixing, amorphous dye particles of colloidal dimensions are formed. We propose that as the dye solution enters the reactor, it is rapidly dispersed into the aqueous phase in the form of small droplets. Counter-diffusion of water and organic solvent occurs within each droplet, leading to rapid precipitation of dye as an amorphous phase. The particles are then stabilized and dispersed uniformly in the reactor.; This mechanism is supported by the observation that the particle formation rate correlates with the local supersaturation $xx*$ where x is the dye concentration in the feed and x* is the solubility of the amorphous dye in the bulk solution. The relationship holds with a variety of solvents and mixing conditions. Since the particle formation rate is determined by the local supersaturation ratio, the size and number of the particles is controllable in this process.; Other organic materials were studied, and they also precipitated as amorphous particles using the solvent shifting technique. Equilibrium solubility measurements of the crystalline solid, together with the free energy of melting, are used to predict the equilibrium solubility of the amorphous phase and the degree of supersaturation during the precipitation process.; The effect of process variables on particle growth rates was also studied. The results of these experiments support growth by diffusion-controlled ripening from molecular mass transport.; The effect of mixing intensity during solvent shifting on particle size was examined. Observations suggest that decreasing the initial droplet size of the feed solution will increase the number of particles formed when the initial droplet diameter approaches the length scale of diffusion into the droplet.