Exploring Sublimation as a Tool for Polymorphic Screening in Niflumic Acid−Caffeine Pharmaceutical Cocrystals Acebedo-Martínez, Francisco J. Alarcón Payer, Carolina Domínguez Martín, Alicia Frontera, Antonio Prohens, Rafel Barbas, Rafael Choquesillo Lazarte, Duane 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 −CF3 groups positioned on the same side of the NIF molecule. However, Form III exhibits a distinct packing arrangement, featuring embedded −CF3 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 2025-10-26T06:32:55Z 2025-10-26T06:32:55Z 2025-10-07 journal article Acebedo-Martínez, F. J., Alarcón-Payer, C., Domínguez-Martín, A., Frontera, A., Prohens, R., Barbas, R., & Choquesillo-Lazarte, D. (2025). Exploring sublimation as a tool for polymorphic screening in niflumic acid–caffeine pharmaceutical cocrystals. Crystal Growth & Design, acs.cgd.5c01007. https://doi.org/10.1021/acs.cgd.5c01007 https://hdl.handle.net/10481/107439 10.1021/acs.cgd.5c01007 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional American Chemical Society