Crystal size distribution and morphology control of sea urchin-like crystal by using irreversibility of external shape change

Abstract

Complex morphology crystals are undesirable due to concerns about crystal size distribution (CSD) and purity drop during reactive crystallization for pharmaceutical production. In the case of cooling crystallization, improvement of CSD by generating inner seed crystals using modulation operations has been reported. As for the morphology, it can be modified by modulation operations with undersaturation. Herein, the effect of this operation to generate inner seed crystals in a reactive crystallization on the characteristics of the product crystals was investigated. As a results, the modulation operation designed under the constraining conditions was the undersaturation operation that resulted in a trade-off relationship between CSD and the morphology. And comparing the results with the standard operation, it is clear that the modulation operation was effective in improving the CSD. In summary, the characteristics of the crystals when using the modulation operation with undersaturation in reactive crystallization could be systematically understood.