Crystallization of Esomeprazole Magnesium Water/Butanol Solvate
1
Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, ON N6A 3K7, Canada
2
Apotex Pharmachem Inc., 34 Spalding Drive, Brantford, ON N3T 6B8, Canada
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Academic Editor: Derek J. McPhee
Molecules 2016, 21(4), 544; https://doi.org/10.3390/molecules21040544
Received: 15 March 2016
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Revised: 8 April 2016
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Accepted: 21 April 2016
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Published: 23 April 2016
(This article belongs to the Special Issue Crystallization of Pharmaceuticals)
The molecular structure of esomeprazole magnesium derivative in the solid-state is reported for the first time, along with a simplified crystallization pathway. The structure was determined using the single crystal X-ray diffraction technique to reveal the bonding relationships between esomeprazole heteroatoms and magnesium. The esomeprazole crystallization process was carried out in 1-butanol and water was utilized as anti-solvent. The product proved to be esomeprazole magnesium tetrahydrate with two 1-butanol molecules that crystallized in P63 space group, in a hexagonal unit cell. Complete characterization of a sample after drying was conducted by the use of powder X-ray diffraction (PXRD), 1H-nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), infrared spectroscopy (IR), and dynamic vapor sorption (DVS). Investigation by 1H-NMR and TGA has shown that the solvent content in the dried sample consists of two water molecules and 0.3 butanol molecules per esomeprazole magnesium molecule. This is different from the single crystal X-ray diffraction results and can be attributed to the loss of some water and 1-butanol molecules stabilized by intermolecular interactions. The title compound, after drying, is a true solvate in terms of water; conversely, 1-butanol fills the voids of the crystal lattice in non-stoichiometric amounts.
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Keywords:
pharmaceutical solvates; solid-state analysis; single crystal X-ray diffraction; thermal analysis; crystallization
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MDPI and ACS Style
Skieneh, J.; Khalili Najafabadi, B.; Horne, S.; Rohani, S. Crystallization of Esomeprazole Magnesium Water/Butanol Solvate. Molecules 2016, 21, 544. https://doi.org/10.3390/molecules21040544
AMA Style
Skieneh J, Khalili Najafabadi B, Horne S, Rohani S. Crystallization of Esomeprazole Magnesium Water/Butanol Solvate. Molecules. 2016; 21(4):544. https://doi.org/10.3390/molecules21040544
Chicago/Turabian StyleSkieneh, Jenna, Bahareh Khalili Najafabadi, Stephen Horne, and Sohrab Rohani. 2016. "Crystallization of Esomeprazole Magnesium Water/Butanol Solvate" Molecules 21, no. 4: 544. https://doi.org/10.3390/molecules21040544
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