Exploring the Crystal Structure Landscape of Sulfasalazine through Various Multicomponent Crystals

Area of Science:

• Solid-state chemistry
• Crystallography
• Pharmaceutical science

Background:

• Sulfasalazine is an anti-inflammatory drug used for inflammatory bowel disease and rheumatoid arthritis.
• Two known solid-state tautomers of sulfasalazine exist: amide (triclinic) and imide (monoclinic).

Purpose of the Study:

• To synthesize and characterize new multicomponent solid forms of sulfasalazine.
• To investigate the structural features and tautomeric behavior of sulfasalazine in cocrystals and salts.
• To analyze the intermolecular interactions and chemical stability of the new solid forms.

Main Methods:

• Slurry crystallization, liquid-assisted grinding, and slow evaporation techniques were employed.
• Characterization involved X-ray diffraction, thermal analysis, and Fourier transform infrared spectroscopy.
• Crystal structure analysis and Hirshfeld surface analysis were performed.

Main Results:

• Six new multicomponent solids (three cocrystals, three salts) of sulfasalazine were successfully crystallized.
• A recurring structural motif, an R2^2(7):R2^2(8):R2^2(7) arrangement, was identified in all new forms and the imide polymorph.
• Sulfasalazine adopted the amide tautomer in unsolvated crystals and the imide tautomer in solvated cocrystals and salts.
• Cocrystals showed significant hydrogen bond donor capability, while salts acted as hydrogen bond acceptors.
• Cocrystals demonstrated greater chemical stability compared to salts.

Conclusions:

• New multicomponent solids of sulfasalazine were successfully prepared, expanding its solid-state landscape.
• The identified structural motif is crucial for the assembly of sulfasalazine in various solid forms.
• Tautomeric behavior is influenced by solvation and the presence of cocrystal or salt formers.
• Cocrystals of sulfasalazine offer enhanced chemical stability, suggesting potential therapeutic advantages.