Exploring Tyramine's Role in the Formation of Supramolecular Adducts with Nonsteroidal Anti‐Inflammatory Drugs

Chiara Rosso,Rebecca Birolo,Angelo Gallo,W. T. Franks,E. Priola,M. R. Chierotti,Roberto Gobetto

Published 2025 in Chemistry

ABSTRACT

Abstract In pharmaceutical crystal engineering, salification and co‐crystallization are well‐established strategies to enhance the physicochemical properties of nonsteroidal anti‐inflammatory drugs (NSAIDs), which typically exhibit low aqueous solubility. This study introduces three new multicomponent crystalline systems of NSAIDs (S‐naproxen, flurbiprofen, and ketoprofen) with the co‐former tyramine, designed using knowledge‐based methods. Additionally, a new polymorph of the diflunisal–tyramine system, synthesized via mechanochemical techniques, is reported. The new multicomponent systems were thoroughly characterized using solid‐state NMR and single‐crystal X‐ray diffraction. Aqueous solubility tests conducted through solution 1H NMR experiments revealed increased equilibrium solubility for all samples, highlighting the efficacy of crystal engineering in modulating the physicochemical properties of drugs.

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