Co-Crystal Structures of Furosemide:Urea and Carbamazepine:Indomethacin Determined from Powder X-Ray Diffraction Data

Abstract

Co-crystallization is a promising approach to improving both the solubility and the dissolution rate of active pharmaceutical ingredients. Crystal structure determination from powder diffraction data plays an important role in determining co-crystal structures, especially those generated by mechanochemical means. Here, two new structures of pharmaceutical interest are reported: a 1:1 co‑crystal of furosemide with urea formed by liquid-assisted grinding and a second polymorphic form of a 1:1 co‑crystal of carbamazepine with indomethacin, formed by solvent evaporation. Energy minimization using dispersion-corrected density functional theory was used in finalizing both structures. In the case of carbamazepine:indomethacin, this energy minimization step was essential in obtaining a satisfactory final Rietveld refinement.

Pharmaceutical Salts of Fenbendazole with Organic Counterions: Structural Analysis and Solubility Performance

“…As the next step, the correctness or accuracy of the structural models obtained for the single-crystal and powder XRD methods was further validated by the DFT-D method in the Quantum ESPRESSO program. , This procedure is recognized as an essential step in structure refinement, especially for the structures solved on the basis of powder diffraction data. ,− The geometry optimization by DFT-D is expected to reconcile the bond lengths and conformation of the molecules/ions with their supramolecular surroundings, to improve the metrics of the intermolecular contacts or to resolve the disorder . Moreover, since the positions of the hydrogen atoms cannot be correctly identified on the basis of powder diffraction, the periodic DFT calculations on powder crystal structures can be used as a valuable tool for refining the hydrogen sites, providing the ultimate grounds for discrimination between cocrystals and salts. , According to van de Streek and Neumann, structures are considered to be correct if the root-mean-square deviation (RMSD) in non-hydrogen atoms between experimental and optimized structures is less than 0.25 Å for a single-crystal structure and 0.35 Å for a powder structure.…”

Theoretical Calculation and Structural Analysis of the Cocrystals of Three Flavonols with Praziquantel

“…To improve the working efficiency and lower the cost, many researchers have adopted the theory of computational chemistry to attempt the virtual screening of a cocrystal. At present, some methods, such as the analysis of the molecular electrostatic potential surfaces (MEPS), are based on density functional theory (DFT), and these methods are used to conduct qualitative and quantitative analyses of the weak interaction between different molecules. − Although the predicted results from these methods are sometimes not ideal due to the relatively simple calculation method and the few influential factors considered, these processes provide a feasible way for researchers to more efficiently study cocrystal formation.…”

Structure Determination of Multicomponent Crystalline Phases of (S)-Ibuprofen and l-Proline from Powder X-ray Diffraction Data, Augmented by Complementary Experimental and Computational Techniques

“…Ibu-Pro was obtained by solid-state mechanochemical synthesis as a microcrystalline powder, and thus structure determination from powder XRD data provides the most viable route to structural characterization. − The powder XRD pattern of Ibu-Pro was indexed using the program TREOR in the CRYSFIRE package, giving the following unit cell with monoclinic metric symmetry: a = 14.43 Å, b = 5.81 Å, c = 21.81 Å, β = 97.10°, V = 1814 Å 3 . As Ibu-Pro contains single enantiomers of ( S )-ibuprofen and l -proline, the space group must be chiral ( P 2, P 2 1 , or C 2).…”