Mechanochemical Synthesis of Resveratrol–Piperazine Cocrystals

Autor: Raul-Augustin Mitran, Simona Ioniţă, Daniel Lincu, Elena Mirabela Soare, Irina Atkinson, Adriana Rusu, Jeanina Pandele-Cuşu, Coca Iordache, Ingemar Pongratz, Mihaela Maria Pop, Victor Fruth
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Materials, Vol 17, Iss 13, p 3145 (2024)
Druh dokumentu: article
ISSN: 1996-1944
DOI: 10.3390/ma17133145
Popis: The 1:1 resveratrol–piperazine cocrystal was successfully synthesized and scaled-up to 300 g scale with the mechanochemical method, as a result of investigating key process parameters, namely the solvent and the grinding time. The use of water, ethanol or ethanol–water mixtures and reaction times up to 50 min were evaluated relative to the dry grinding process. Cocrystal formation and purity were monitored through X-ray diffraction and calorimetry measurements. The dry grinding resulted in an incomplete cocrystal formation, while the use of water or water–ethanol mixture yielded a monohydrate solid phase. Pure ethanol was found to be the optimal solvent for large-scale cocrystallization, as it delivered cocrystals with high crystallinity and purity after 10–30 min grinding time at the laboratory scale. Notably, a relatively fast reaction time (30–60 min) was sufficient for the completion of cocrystallization at larger scales, using a planetary ball mill and a plant reactor. Also, the obtained cocrystal increases the aqueous solubility of resveratrol by 6%–16% at pH = 6.8. Overall, this study highlights the potential of solvent-assisted mechanochemical synthesis as a promising new approach for the efficient production of pure resveratrol–piperazine cocrystals.
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