Crystallization of Esomeprazole Magnesium Water/Butanol Solvate.
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.
Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, ON N6A 3K7, Canada. jskieneh@uwo.ca.
Jenna
J
Skieneh
Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, ON N6A 3K7, Canada. bkhalili@uwo.ca.
Bahareh
B
Khalili Najafabadi
Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, ON N6A 3K7, Canada. shornehome@gmail.com.|Apotex Pharmachem Inc., 34 Spalding Drive, Brantford, ON N3T 6B8, Canada. shornehome@gmail.com.
Stephen
S
Horne
Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, ON N6A 3K7, Canada. srohani@uwo.ca.
Sohrab
S
Rohani
D000440:Butanols / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray; D064098:Esomeprazole / Q000737:chemistry*; D006860:Hydrogen Bonding; D015394:Molecular Structure
D000440:Butanols; D064098:Esomeprazole
crystallization; pharmaceutical solvates; single crystal X-ray diffraction; solid-state analysis; thermal analysis