Application of temperature cycling for crystal quality control during crystallization

Abstract

Characteristics of crystal quality, including crystal size distribution, size, morphology, polymorphism and chirality, have been established as important indicators of crystalline materials. There have been many attempts at controlling crystal quality during crystallization. Herein, this study summarizes crystal quality control by using temperature cycling during solution state crystallization. During crystallization, the temperature cycling is implemented through successive heating–cooling cycles for dissolution and recrystallization in crystal suspension. Therefore, the fines crystals or one species are expected to dissolve out completely during the heating period, and the remaining crystals or dominant species continuously grow or nucleate during the cooling period. When such temperature cycling is facilitated during crystallization, the characteristics of crystal quality, including crystal size distribution, size, morphology, polymorphism and chirality, are well managed. Furthermore, based on the basic principle of temperature cycling, the key parameters for controlling each characteristic of crystal quality are clearly elucidated during the process. Thus, this review provides qualitative insight into the general operation strategies and the principle of temperature cycling for crystal quality control during crystallization.