Premium
The mechanism of solvent‐mediated desolvation transformation of lenvatinib mesylate from dimethyl sulfoxide solvate to form D
Author(s) -
Zheng Zhixin,
Hou Baohong,
Cheng Xiaowei,
Liu Wanying,
Huang Xin,
Bao Ying,
Wang Ting,
Wang Zhao,
Hao Hongxun
Publication year - 2020
Publication title -
acta crystallographica section b
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.604
H-Index - 33
ISSN - 2052-5206
DOI - 10.1107/s2052520620003935
Subject(s) - dimethyl sulfoxide , differential scanning calorimetry , thermogravimetric analysis , solubility , solvent , chemistry , raman spectroscopy , sulfoxide , phase (matter) , nucleation , gravimetric analysis , chemical engineering , crystallography , organic chemistry , thermodynamics , physics , optics , engineering
In this work, the mechanism of solvent‐mediated desolvation transformation of lenvatinib mesylate (LM) was investigated. Two new solid forms of LM, a dimethyl sulfoxide (DMSO) solvate and an unsolvated form defined as form D, were discovered and characterized using powder X‐ray diffraction, thermogravimetric analysis, differential scanning calorimetry, polarized light microscopy and Raman spectroscopy. To investigate the thermodynamic mechanism of solvent‐mediated desolvation transformation (SMDT) from LM DMSO solvate to form D, solubilities of LM DMSO solvate and form D in binary solvent mixtures of DMSO and water at different water volume fractions and temperatures (293.15–323.15 K) were measured and correlated by non‐random two liquids model. The solubility data were used to evaluate the thermodynamic driving force of the SMDT process from DMSO solvate to form D and the effect of the activities of water and DMSO on the transformation process. Raman spectroscopy was used to monitor in situ the solid phase compositions during the SMDT process from LM DMSO solvate to form D while the solution concentration was measured by the gravimetric method. The overall desolvation transformation experiments demonstrated that the SMDT process was controlled by the nucleation and growth of form D. Moreover, effects of operating factors on the SMDT process were studied and the results illustrated that water activity in solution was the paramount parameter in the SMDT process. Finally, a new SMDT mechanism was suggested and discussed.