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

Abstract

Two multicomponent crystalline phases of (S)-ibuprofen and L-proline with 1:1 stoichiometry are reported, specifically a nonsolvate phase (Ibu-Pro) and a quarter-hydrate phase (Ibu-Pro-QH). Ibu-Pro was prepared only by solid-state mechanochemical synthesis, while Ibu-Pro-QH was obtained both by solution-state crystallization and by solid-state mechanochemistry. The crystal structures of Ibu-Pro and Ibu-Pro-QH were determined directly from powder X-ray diffraction (XRD) data, with structure solution carried out using the direct-space strategy (implemented with a genetic algorithm search procedure) and structure refinement carried out using the Rietveld method. The process of structure determination from powder XRD data was augmented by information from other complementary techniques, specifically solid-state NMR spectroscopy, thermal analysis methods, and periodic DFT-D calculations. A preliminary powder XRD study of the dehydration behavior of Ibu-Pro-QH at elevated temperature is also reported.

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

“…The Kohn–Sham methods with periodic boundary conditions (periodic DFT) provided a grounded tradeoff between the accuracy and the rate of calculations of the experimentally observed properties of multicomponent organic crystals. − Multicomponent crystals of pharmaceutical use often consist of ionic/zwitterionic species, − which interact with neighboring molecules by short (strong) or ionic H-bonds . B3LYP and dispersion-corrected PBE are usually used in periodic DFT computations with an all-electron Gaussian-type localized orbital basis, while PBE-D3 is usually explored with the plane-wave basis sets. , Very recently, we have shown that B3LYP and PBE-D3 with fixed cell parameters provide a reasonable description of the low-frequency Raman spectra of multicomponent crystalline forms of anthelmintic drugs .…”

Multicomponent Crystal of Trimethoprim and Citric Acid: Solid State Characterization and Dissolution Rate Studies

“…X-ray diffraction analysis is a technique to characterize the solid properties of active pharmaceutical compounds. Changes in the X-ray diffraction pattern in solids resulting from intramolecular interactions indicate the formation of new crystalline phases such as cocrystals or salts [18]. Figure 1 presents the X-ray diffraction pattern of trimethoprim, citric acid, and the multi-component crystalline phase.…”

Structural features, dissolution performance and anthelmintic efficacy of multicomponent solid forms of fenbendazole with maleic and oxalic acids

“…Thus, the process of structure determination from powder XRD is usually complemented by periodic DFT-D calculations, which improve metric parameters of covalent bonds and non-covalent interactions as well as reconcile the proton sites with an actual crystalline environment. [73][74][75][76][77][78] The latter aspect is essential for discrimination between cocrystals and salts in multicomponent structures where the extent of proton transfer is uncertain. 68,79 In this study, the PBE-D3 geometry optimization (with fixed unit cell) was applied to enhance the accuracy of the structural models obtained via powder XRD data.…”