Production of sodium chloride crystals of uni-modal size distribution by batch dilution crystallization

The strategy of producing crystals of uni-modal size distribution was investigated for dilution (or anti-solvent) crystallization. Sodium chloride was crystallized as a model compound from aqueous solution by adding pure ethanol (99 vol.% ethanol) or an ethanol-water (75 vol.% ethanol) mixture as diluent. The effects of external seeding on the product CSD were clearly observed. At high external-seed loadings, uni-modal product crystals of grown seeds were obtained with virtually no nucleation. However, at low external-seed loadings, primary as well as secondary nucleation occurred, so that product crystals with bi-modal size distribution were obtained. This primary nucleation was considered to be due to high local concentration of ethanol (or high local supersaturation) created near the nozzle, through which the diluent was injected. By the addition of the pure ethanol into the non-seeded saturated aqueous solution, fine crystals with an identical uni-modal narrow size distribution were obtained, irrespective of the amount of the diluent added. These fine crystals were grown successfully as internal seeds to product crystals with uni-modal size distribution. This internal seeding is expected to be a promising "seeding" technique in the pharmaceutical industry, where external seeding is not favored.