2025/10/07 by F.J. Acebedo-Martínez, Carolina Alarcón-Payer, Alicia Domínguez‐Martín +4 · 3 voices
Chemistry · Materials Science · #Analytical Chemistry and Chromatography #Crystallization and Solubility Studies #Crystallography and molecular interactions
paper · doi:10.1021/acs.cgd.5c01007
openalex publication_date 2025/10/07 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/02
High Resolution Image Download MS PowerPoint Slide Sublimation has emerged as a powerful tool for polymorphic screening in pharmaceutical multicomponent materials. In this work, a combined strategy involving mechanochemistry and sublimation enables the selective synthesis and isolation of a novel polymorph ( Form III ) of the niflumic acid–caffeine ( NIF–CAF ) cocrystal. Solid-state characterization and complementary theoretical studies revealed that Form III is morphotropically related to Form II, sharing a similar molecular conformation with the −COOH and −CF 3 groups positioned on the same side of the NIF molecule. However, Form III exhibits a distinct packing arrangement, featuring embedded −CF 3 groups and alternating molecular tapes stabilized by π–π and F···F interactions. Thermal analysis also indicates an enantiotropic relationship between Forms II and III, with Form III becoming the more stable phase above the estimated transition temperature of ∼102 °C, and showing a melting point of 156 °C. These findings demonstrate the relevance of sublimation in polymorphic screening and its potential to expand the solid-state landscape of multicomponent materials with enhanced control and reproducibility.