Regarding sugar and salt crystallization with large single crystals, the agglomerate thermodynamics and geometric morphologies, not the dynamics, dominate the particle size distribution (PSD). To consider this issue, a PSD design model is proposed for limited large crystal agglomeration. In this model, the agglomeration thermodynamic criticality is determined by estimating the adhesion and dispersion forces between single crystals. The geometric agglomerate morphologies are described by corresponding single crystal units stacking with porosity. By seed well-controlled of population, the key parameters of PSD (D01, D50 and D99) are precisely designed. For erythritol, the model design accuracies are 92%-99% in the 1.2 L and 10 L crystallizers, indicating that it can design PSD at various crystallization scales. Concerning the general research attention to microcrystal agglomeration kinetics (mostly active pharmaceutical ingredients), this model effectively guides the sugar and salt PSD design with limited large crystal agglomeration.

In recent studies, the existence of mesoscale precursors has been confirmed in crystallization. Different from the classical crystallization theory, which only considers the sequential attachment of basic monomers (atoms, ions, or molecules), the nonclassical crystallization process involving precursors such as prenucleation clusters, nanoparticles, and mesocrystals is more complicated. The mesoscale structure is important for the quantitative description and directional regulation of the solution crystallization process. It is necessary to explore the mechanism by the mesoscale scientific research methods on the base of traditional chemical engineering and process system engineering research methods. Therefore, the paper reviews several representative nonclassical nucleation and growth theories, mainly including two-step nucleation theory, prenucleation clusters theory, particle agglomeration theory, amorphous precursor growth theory, particle attachment growth theory and mesocrystal growth theory. Then, the mesoscale structure and its spatiotemporal dynamic behavior are discussed, and the application of the EMMS model in the nucleation and growth process is analyzed. Finally, we put forward our views on the prospect of the paradigms and theoretical innovations of using mesoscale methods in crystal nucleation and growth.

The citrate industry has a wide range of applications in food, pharmaceutical, and other fields. As a common class of food additives and functional supplements with tremendous development potential and strong core competitiveness, particles with good powder characteristics and functionalization are becoming one of the primary directions in the evolution of citrate into the high-end market. This article reviews the primary citrate crystallization techniques and examines the fundamental citrate crystallization mechanisms by describing citrate nucleation and growth during the industrial crystallization process. A variety of citrate hydrates are also summarized. The primary control conditions of the three essential product indices of purity, particle size, and grain shape are established. The need to take into account the density, fluidity, caking resistance, dissolution rate, suspension, bioavailability, and other indices of products is highlighted, along with applications for products that meet the purity and particle size requirements. While summarizing industrial citrate crystallization equipment, this paper also discusses the beneficial effect of continuous crystallization in achieving industrialization. Finally, the future development of citrate crystals is anticipated, and it is suggested that the combination of basic research and application research should be strengthened to explore the new application field of citrate crystals, and the automation and intelligence of the crystal preparation process should be realized as far as possible.