ArticlePharmaceutical research2026
Trimorphism in riluzole salicylate: screening, crystal structures and solution thermodynamics.
Article in Pharmaceutical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeThis study investigated the phenomenon of polymorphism in the pharmaceutical salt riluzole salicylate with the aim to modify the aqueous solubility and dissolution rate of riluzole.
methodsPreparation routes and transformation pathways were investigated using mechanoactivation, sonication, sublimation and melt crystallization. The thermal-induced phase transformations were interpreted by thermal microscopy and ex situ PXRD analysis. The crystal structure of Form 3 was solved from powder diffraction data. The differences in non-covalent interactions in crystals of Form 1 and Form 3 and their role in structure stabilization were studied by QTAIMC analysis, fingerprint plots, energy frameworks and lattice energy calculations. Cocrystallization thermodynamic functions and relationships between three polymorphs were established based on DSC, solubility and lattice energy data.
resultsTwo novel polymorphs of riluzole salicylate with higher melting points were discovered and characterized in addition to reported Form 1. The stable Form 3 can be obtained easily by milling or from the slurry, while the metastable Form 2 forms only by melt crystallization or resublimation. Form 3 has stronger hydrogen bonding and more balanced non-covalent interactions than Form 1, making it thermodynamically favored at room temperature, while Form 1 is more stable near absolute zero.
conclusionPolymorphism significantly affects the pharmaceutical properties of riluzole salicylate. Selective preparation of polymorphs enables tuning of solubility and dissolution, linking crystal structure and thermodynamics to drug delivery optimization. Slower release kinetics of Form 1 compared to Form 3 and parent RLZ indicates its potential use as a prolonged form.
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