Chinese Journal of Chemical Engineering ›› 2020, Vol. 28 ›› Issue (4): 935-948.doi: 10.1016/j.cjche.2019.11.008

• Reviews •     Next Articles

Recent advances of pharmaceutical crystallization theories

Jingyun Weng, Yiping Huang, Dule Hao, Yuanhui Ji   

  1. Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China
  • Received:2019-07-25 Revised:2019-11-20 Online:2020-04-28 Published:2020-07-27
  • Contact: Yuanhui Ji
  • Supported by:
    This work was financially supported by the National Natural Science Foundation of China (Grant Nos. 21776046 and 21606043), the Six Talent Peaks Project in Jiangsu Province (Grant No. XCL-079), the Fundamental Research Funds for the Central Universities (Grant No. 2242019K40145), and the Recruitment Program for Young Professionals (the Thousand Youth Talents Plan).

Abstract: As a technology of separation and purification, crystallization plays a vital role in diverse industries such as inorganic salt, pharmaceutical, and food industries, which has a huge impact on purity, crystal polymorph, crystal morphology, and particle size distribution of final products. In the past few decades, with the rapid advancement of experimental approaches and molecular simulation methods, considerable advances in the interpretation of crystallization mechanisms have been obtained, promoting the investigation and understanding of crystallization theories greatly. In this review, the advances of pharmaceutical crystallization theories in recent years from the perspectives of nucleation and crystal growth are summarized and discussed. Two thermodynamic models that are helpful in the study of the crystallization mechanisms will be introduced. In this section, the perturbed-chain statistical associating fluid theory (PC-SAFT) and a chemical-potential-gradient model will be introduced, which have been successfully applied in pharmaceutical solubility prediction, the research of dissolution mechanism as well as dissolution kinetics analysis. These two models are expected to be applied to the study of pharmaceutical crystallization process and mechanism. Furthermore, molecular simulation based on the interaction between particles can provide structural information, thermodynamics, and dynamics properties of complex systems at the molecular level, like intermolecular interaction and surface adsorption energies. Application and some shortcomings of molecular simulation, especially molecular dynamics simulation, in the field of pharmaceutical crystallization will be expounded.

Key words: Nucleation, Crystal growth, Thermodynamics, Molecular simulation