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

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.