Mechanochemical Synthesis of Resveratrol-Piperazine Cocrystals

• Published in: Materials 2024-06, Vol.17 (13), p.3145
• Main Authors: Mitran, Raul-Augustin, Ioniţă, Simona, Lincu, Daniel, Soare, Elena Mirabela, Atkinson, Irina, Rusu, Adriana, Pandele-Cuşu, Jeanina, Iordache, Coca, Pongratz, Ingemar, Pop, Mihaela Maria, Fruth, Victor
• Format: Article
• Language: English
• Subjects: Antibiotics; Bioavailability; Cocrystallization; Drug resistance; Dry grinding; Ethanol; Microscopy; Mixtures; Polyphenols; Process parameters; Purity; Reaction time; Solid phases; Solvents; Spectrum analysis
• ISSN: 1996-1944; 1996-1944
• DOI: 10.3390/ma17133145

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.