Journal
JOURNAL OF CRYSTAL GROWTH
Volume 463, Issue -, Pages 168-175Publisher
ELSEVIER
DOI: 10.1016/j.jcrysgro.2017.02.028
Keywords
Ionic liquids; Crystallization; Aspect ratio; Organic solvents; Hydrogen bonding
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The pharmaceutical crystallization is quite challenging in terms of the target properties like desired habit or morphology, size and the size distribution of the resultant crystals. Controlling the dimensions along the crystallographic axes, especially for the crystals with needle shape, is desired for operational flexibility. There has been a great interest in using Ionic Liquids (ILs) as a novel crystallization media, but inter molecular interaction between ILs and pharmaceutical solids are quite complex. Interactions in ionic media can be tuned to achieve target physical properties. In this study, ibuprofen is crystallized using imidazolium based IL with PF6 anion, which produces needle shaped crystals with high aspect ratio. It is found that aspect ratio is significantly altered when a small quantity of organic solvents is added to the crystallizing media. These organic solvents prefer to interact with certain domain of IL and this interaction can be utilized in achieving the objective of reduction in aspect ratio. Use of methanol and 2-ethoxy ethyl acetate is found to provide a significant reduction in aspect ratio. The role of hydrogen bonding ability of C-2 hydrogen of imidazolium ionic liquid in steering the crystal shape is discussed. (C) 2017 Elsevier B.V. All rights reserved.
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