Abstract

For continuous crystallization of pharmaceutical and organic chemical compounds in a plug flow crystallizer, seed slurry, prepared in advance, is continuously fed into the crystallizer for controlled secondary nucleation and subsequently desired crystal properties. It is well known that the preparation of macro seed crystals using either the dry or wet method is a highly time-, energy- and material-intensive process, often taking many hours to prepare a 1 L seed slurry. The focus of this work is to examine whether how the seed slurry is made up could have any effect on the final crystal properties. We divide the seed slurry into two parts: the “saturation part” corresponds to the amount of solute required to establish solid–liquid equilibrium and is fully dissolved, and the “supersaturation part” involves a small amount of solid seed crystals in excess of the equilibrium saturation condition. The hypothesis states that if dissolved seed crystals have lost their surface properties (such as size, morphology, interfacial effects), the final crystal size distributions would then inherit that of the solid seed crystals. If this is true, this would provide a great and efficient shortcut for the lengthy and energy-intensive process of making up seed slurries, as product crystals from a previous batch of any size distribution could be used for the make-up of the saturation part of the seed slurry. Using adipic acid and L-glutamic acid with high and low solubilities, the hypothesis has been validated experimentally under batch conditions.

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