(707e) Crystallization of Valnemulin Hydrochloride Heterosolvate: Crystal Structure, Desolvation Behavior, Solubility and Nucleation Mechanism

Authors: 
Hao, H. - Presenter, Tianjin university, Tianjin, China
Wang, J. - Presenter, National Engineering Research Center for Industrial Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University

In this article, a new heterosolvate of valnemulin hydrochloride (HS-VLMHCl) was discovered and successfully prepared in ethanol solution of amorphous valnemulin hydrochloride (VLMHCl). Powder X-ray diffraction (PXRD) and thermal gravimetric analysis (TGA) were applied to characterize HS-VLMHCl. The crystal structure was determined by single-crystal X-ray diffraction for the first time, and it was found that both water and ethanol molecules participated in the forming crystal lattice with VLMHCl molecule ratio of 1:1:1. The result was also verified by thermal analysis and desolvation behavior successfully. To understand crystallization behavior of HS-VLMHCl, the solubility of HS-VLMHCl in water, methanol, ethanol, isopropanol, acetone, ethyl acetate were experimentally determined from 278.15 to 313.15 K using a static analytical method. In addition, the dissolution thermodynamic properties of HS-VLMHCl, including dissolution enthalpy and dissolution entropy in all test solvents, were obtained by using van’t Hoff equation. Furthermore, the nucleation kinetic of HS-VLMHCl in ethanol system was investigated. The induction time was measured at 278.15 K, 283.15K, 288.15K at different supersaturation, and interfacial energies were calculated by using classical nucleation theory. The results reveal that nucleation process includes two steps: homogeneous nucleation and heterogeneous nucleation. The heterogeneous nucleation is the main mechanism at a low supersaturation, while the homogeneous nucleation predominates at a high supersaturation.