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Mechanochemical synthesis insights and solid‐state characterization of quininium aspirinate, a glass‐forming drug–drug salt
Author(s) -
Harris Nehemiah,
Benedict Jubilee,
Dickie Diane A.,
Pagola Silvina
Publication year - 2021
Publication title -
acta crystallographica section c
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.304
H-Index - 17
ISSN - 2053-2296
DOI - 10.1107/s2053229621008275
Subject(s) - differential scanning calorimetry , thermogravimetry , materials science , amorphous solid , mechanochemistry , powder diffraction , crystallization , ball mill , crystallography , chemical engineering , chemistry , organic chemistry , inorganic chemistry , metallurgy , nanotechnology , physics , engineering , thermodynamics
Quinine (an antimalarial) and aspirin (a nonsteroidal anti‐inflammatory drug) were combined into a new drug–drug salt, quininium aspirinate, C 20 H 25 N 2 O 2 + ·C 9 H 7 O 4 − , by liquid‐assisted grinding using stoichiometric amounts of the reactants in a 1:1 molar ratio, and water, EtOH, toluene, or heptane as additives. A tetrahydrofuran (THF) solution of the mechanochemical product prepared using EtOH as additive led to a single crystal of the same material obtained by mechanochemistry, which was used for crystal structure determination at 100 K. Powder X‐ray diffraction ruled out crystallographic phase transitions in the 100–295 K interval. Neat mechanical treatment (in a mortar and pestle, or in a ball mill at 20 or 30 Hz milling frequencies) gave rise to an amorphous phase, as shown by powder X‐ray diffraction; however, FT–IR spectroscopy unambiguously indicates that a mechanochemical reaction has occurred. Neat milling the reactants at 10 and 15 Hz led to incomplete reactions. Thermogravimetry and differential scanning calorimetry indicate that the amorphous and crystalline mechanochemical products form glasses/supercooled liquids before melting, and do not recrystallize upon cooling. However, the amorphous material obtained by neat grinding crystallizes upon storage into the salt reported. The mechanochemical synthesis, crystal structure analysis, Hirshfeld surfaces, powder X‐ray diffraction, thermogravimetry, differential scanning calorimetry, FT–IR spectroscopy, and aqueous solubility of quininium aspirinate are herein reported.