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

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 authors emails:
DOI10.24435/materialscloud:2020.0014/v1 [version v1]

Publication date: Jan 28, 2020

How to cite this record

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 2020.0014/v1 (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
226.7 MiB Plumed input and COLVAR files obtained from the simulations.
1.1 KiB Description of the inh-dandan.tar.gz files


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

Version history:

2020.0014/v1 (version v1) [This version] Jan 28, 2020 DOI10.24435/materialscloud:2020.0014/v1