Solvent-mediated morphology selection of the active pharmaceutical ingredient isoniazid: Experimental and simulation studies

Authors: Dandan Han1, Tarak Karmakar2, Zoran Bjelobrk3, Junbo Gong1, Michele Parrinello2*

  1. School of Chemical Engineering and Technology, Tianjin University, Collaborative Innovation Center of Chemistry Science and Engineering, Tianjin 300072, China
  2. Department of Chemistry and Applied Biosciences, ETH Zürich, CH-8093 Zürich and Facoltà di informatica, Istituto di Scienze Computazionali, Università della Svizzera Italiana, CH-6900 Lugano, Switzerland
  3. Institute of Process Engineering, ETH Zürich, CH-8093 Zürich, Switzerland
  • Corresponding author email:

DOI10.24435/materialscloud:2020.0014/v1 (version v1, submitted on 28 January 2020)

How to cite this entry

Dandan Han, Tarak Karmakar, Zoran Bjelobrk, Junbo Gong, Michele Parrinello, Solvent-mediated morphology selection of the active pharmaceutical ingredient isoniazid: Experimental and simulation studies, Materials Cloud Archive (2020), doi: 10.24435/materialscloud:2020.0014/v1.


In solution crystallization, solvent has a profound effect on controlling crystal morphology. However, the role played by solvents in affecting crystal morphology remains elusive. Here, we accompany experiments with molecular dynamics simulations to investigate crystallization of an anti-tuberculosis drug, isoniazid, in different solvents. Experiments show that isoniazid grows as needle-like crystals in water, while in alcohols such as methanol, ethanol and isopropanol, it exhibits a rod-like crystal habit. The aspect ratio of isoniazid crystals decreases with the decrease in the relative solvent polarity. We modeled these experiments by performing molecular dynamics simulations of isoniazid crystallization in different solvents at constant chemical potential thus keeping the solution concentration constant. The simulation results reveal a rough growth mechanism for the fast growing (1 1 0) surface, and bulk transport of the solute from solution to the growing surface is the limiting-step. In accordance with experiments, the relative growth rate of this surface decreases from methanol, ethanol to isopropanol. On the other hand, the slow growing (0 0 2) surface appears to follow a stepwise growth mechanism, with a surface integration step chiefly controlling the growth. The relative growth rate of this surface increases from methanol to ethanol and isopropanol.

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File name Size Description
MD5MD5: 24ac93c2fbddaca52084c242072d6fd9
226.7 MiB Plumed input and COLVAR files obtained from the simulations.
MD5MD5: c09aa53009c706c6440e9a194794a9d1
1.1 KiB Description of the inh-dandan.tar.gz files


Files and data are licensed under the terms of the following license: Creative Commons Attribution 4.0 International.


ERC MARVEL MARVEL/DD1 Solution crystallization Crystal growth Morphology solvent effect on crystal shape

Version history

28 January 2020 [This version]