Structural Characterization of Pharmaceutical Cocrystals with the Use of Laboratory X-ray Powder Diffraction Patterns

Abstract

X-ray powder diffraction is a vital analytical tool that is used in pharmaceutical science. It is increasingly used to establish the crystal structure of a new pharmaceutical substance, in particular, cocrystal or its polymorphic forms. This review begins with a brief discussion of the reliability of the structural parameters retrieved from powder patterns. Recent examples of the successful determination of crystal structures of pharmaceutical cocrystals and salts from powder diffraction data are discussed. These examples show the increased capabilities of laboratory X-ray powder diffractometers and modern software in solving actual problems of pharmaceutical science.

Structural analysis of anti-retroviral drug raltegravir and its potential impurity C: investigation of solubility and stability

“…In the absence of suitable single crystals of anhydrous RLT form A and impurity C, their crystal structures were determined from the laboratory PXRD data, once again demonstrating the capabilities of laboratory powder diffractometry in the structural characterization of pharmaceutical substances. 32 Most often, either crystals of the RLT hydrate or the precipitate of form C resulted. The crystal structure of impurity C1 was solved from the single crystal XRD, as the corresponding single crystals were obtained (using input impurity C) in MeOH solution.…”

The Peculiar H-Bonding Network of 4-Methylcatechol: A Coupled Diffraction and In Silico Study

“…During the structure determination process, all C -H hydrogen atoms were positioned according to the expected distances dictated by crystallochemistry, as bond angles are strictly governed by the hybridization of the corresponding carbon atoms. However, the positioning of hydrogen atoms associated with alcoholic groups, which is directed by the torsional angle around the C -O bond axis, proved to be unfeasible through Rietveld refinement due to the limited resolution of the technique [43,44]. To address this limitation, first principle calculations were conducted using Gaussian16 to optimize the positions of the hydrogen atoms and achieve a more accurate characterization of the hydrogen bonding network.…”

“…The geometric optimization of the hydroxyl hydrogen atoms was carried out with the Gaussian16 software [47], using the Hartree-Fock method with the 3-21G basis set for approximate positioning. Starting from the optimized structure obtained, DFT calculations were carried out with B3LYP and 6-31G(d,p) basis set level of theory for fine positioning [43,48]. Using the latter setup, single-point energies of the different configurations of the hydrogen bond framework were compared to select the most stable one.…”

Expanding the Crystal Structure Landscape of Pravastatin Complexes: Tuning Solubility, Diffusion, and Pharmacokinetics

“…The molecular structure of PRV−Na−PRO was confirmed using powder XRD data measured at room temperature on the laboratory diffractometer Stoe Stadi-P with curved Ge monochromator (Cu Kα1 radiation), which was successfully used in structure determination of pharmaceutical cocrystals. 37 The powder pattern was indexed in the monoclinic unit cell, and the crystal structure was solved with the use of simulated annealing technique 38 and refined with the program MRIA 39 following the procedure described by us earlier 40,41 (for details, see also Supporting Information). The experimental and calculated diffraction profiles after the final bond-restrained Rietveld refinement are shown in Figure S1, Supporting Information.…”