Repeated Cooling Crystallization for Production of Microcrystals with a Narrow Size Distribution

摘要

The batch cooling crystallization of an organic compound, p-acetanisidide, was carried out using methanol as a solvent and no seed crystal. The crystallization needed an induction period of 10-200 min before nucleation, and the size distribution of the product crystals was broad with sizes ranging from 10 to 270 pm determined as the diameter of a circle with equal projection area. In order to control the nucleation process and obtain microcrystals with a narrow size distribution, the dissolution of crystals obtained by cooling crystallization, followed by recrystallization was adopted. Thus, the crystals once obtained by cooling crystallization were completely dissolved by heating the slurry to a temperature 17°C that was higher than the saturation temperature by 1.5°C. After the solution was maintained at that temperature for a given time, it was cooled again. In the case of repeated crystallization, the induction period observed in the first crystallization disappeared, and small crystals with a mean diameter of 40 pm and a narrow size distribution were obtained. However, the effect of the complete dissolution of crystals on the production of microcrystals with a narrow size distribution disappeared when the solution was incubated at 17°C over 90 min. These results were explained on the basis of the history of the solution structure.