Hydrate vs Anhydrate under a Pressure-(De)stabilizing Effect of the Presence of Water in Solid Forms of Sulfamethoxazole

• Published in: Crystal growth & design Vol. 21; no. 12; pp. 6879 - 6888
• Main Authors: Patyk-Kaźmierczak, Ewa, Kaźmierczak, Michał
• Format: Journal Article
• Language: English
• Published: American Chemical Society 01.12.2021
• ISSN: 1528-7483; 1528-7505
• DOI: 10.1021/acs.cgd.1c00784

An understanding of the structure–properties relationship of crystals is one of the principles of crystal engineering. It is well established that the physicochemical properties of solids, such as their temperature and pressure stability, can be modified by the diversification of the chemical composition: i.e., by the synthesis of multicomponent crystals. This method is widely used in the pharmaceutical industry in the search for novel crystal forms providing higher bioavailability and better processability during the manufacturing process. It is also crucial to thoroughly study, analyze, and compare multicomponent crystals with neat crystals to assess to what extent their properties were altered. In this work we investigate the effect of the presence of water molecules on the pressure stability of crystals, on an example of an antibiotic sulfamethoxazole in its neat form (polymorph I, SMX I) and as a hemihydrate (SMX·0.5H2O). The crystals were investigated under high pressure in a series of hydrostatic media up to ca. 4 GPa. SMX I was established to be the preferred and stable solid form of sulfamethoxazole under the studied conditions, while the compression of crystals of SMX·0.5H2O above 3.7 GPa led to a reversible isostructural solid-to-solid phase transition to phase II (named SMX hemihydrate-II). The difference between SMX hemihydrates I and II and a comparison of the pressure stability of the investigated forms of SMX are discussed in terms of intermolecular interactions, Full Interaction Maps (FIMs), structural voids, and changes in crystal density. It has been shown that lower density and less ordered molecular arrangement in crystals of SMX hemihydrate, a direct effect of the presence of water molecules, contribute to its lower pressure stability in comparison to crystals of SMX I.