Mechanochemical synthesis insights and solid-state characterization of quininium aspirinate, a glass-forming drug-drug salt.
Acta Crystallogr C Struct Chem
; 77(Pt 9): 566-576, 2021 09 01.
Article
in En
| MEDLINE
| ID: mdl-34482301
ABSTRACT
Quinine (an antimalarial) and aspirin (a nonsteroidal anti-inflammatory drug) were combined into a new drug-drug salt, quininium aspirinate, C20H25N2O2+·C9H7O4-, by liquid-assisted grinding using stoichiometric amounts of the reactants in a 11 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 100â
K. Powder X-ray diffraction ruled out crystallographic phase transitions in the 100-295â
K interval. Neat mechanical treatment (in a mortar and pestle, or in a ball mill at 20 or 30â
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 15â
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Quinine
/
Anti-Inflammatory Agents, Non-Steroidal
/
Aspirin
Language:
En
Journal:
Acta Crystallogr C Struct Chem
Year:
2021
Document type:
Article
Affiliation country: