Date Published: July 01, 2020
Publisher: International Union of Crystallography
Author(s): Andrew D. Bond, Changquan C. Sun.
Six isostructural crystalline solvates of celecoxib are reported and the intermolecular interactions involving the solvent molecules are described.
Understanding the structures and properties of crystalline solids can be of significant importance for active pharmaceutical ingredients (APIs) (Sun, 2009 ▸). Solid-form screening is an integral part of most pre-formulation activities (Morissette et al., 2004 ▸), with an aim to establish the range of solid forms that can exist for a given API. These generally include both polymorphs and multicomponent forms, which may variously be described as salts, cocrystals, solvates, etc. (Aitipamula et al., 2012 ▸).
This set of six isostructural celecoxib solvates includes small solvent molecules that can accept hydrogen bonds. The host celecoxib framework is consistent within the set, but it shows quite substantial flexibility in its unit-cell parameters and solvent-accessible void space, and can therefore accommodate solvent molecules of varying size and shape. The crystallographic disorder in several of the structures is understandable on the basis of the local twofold symmetry of the solvent binding site, compared to the point symmetry of the solvent molecules. In the absence of any additional hydrogen-bond donors in the solvent molecules, the next most stabilizing interactions between the solvent molecules and the celecoxib framework are C—H⋯O contacts to the S=O groups. The consideration of PIXEL interaction energies, in combination with geometrical analysis of the crystal structures, is helpful in drawing these conclusions.