Rapid Synthesis and Evaluation of Resveratrol-Piperazine Cocrystals by Ultrasound and Microwave Methods.

Resveratrol-piperazine cocrystals have been obtained by ultrasound (US) and microwave-assisted (MW) techniques, using the solution and slurry-based methods, to study the influence of the synthesis method on the resulting cocrystal properties, and scalability of the processes. The potential of these cocrystals is represented by the unique properties of their components, resveratrol, and piperazine, which could be also used in veterinary practice. Resveratrol has antimicrobial, antiviral and anticarcinogenic properties, while piperazine can be used in the treatment of parasitic infections. The influence of ultrasound and microwave-assisted treatment was studied by varying synthesis parameters such as reaction time, temperature, and US or MW power. The main advantage of using these methods is represented by shorter synthesis time compared to conventional methods, resulting in the direct formation of the cocrystals. All samples were obtained in high purity, above 97%. Cocrystal yield correlated positively with ultrasound reaction time, while temperature was not found to influence the microwave synthesis yield up to 50°C, in the case of solution-based methods. MW and US-assisted solution-based methods lead to yields between 52.9 and 68.1%. In the case of the slurry-based method, a minimum reaction time of 5 min leads to the formation of cocrystals with high purity. The resveratrol-piperazine cocrystal's solubility and in vitro antibacterial activity were also evaluated, showing promising results. Ultrasound and microwave-assisted techniques offer a viable alternative for synthesizing resveratrol-piperazine cocrystals with short reaction times, high yield, and purity, suitable for scalable resveratrol-piperazine cocrystals.

Ioniţă S ，Pătrașcu M ，Soare EM ，Lincu D ，Atkinson I ，Rusu A ，Pop MM ，Iordache C ，Ușurelu CD ，Baltac AS ，Mitran RA ，Pandele-Cuşu J ，Fruth V ... -  《-》

Mechanochemical Synthesis of Resveratrol-Piperazine Cocrystals.

Mitran RA ，Ioniţă S ，Lincu D ，Soare EM ，Atkinson I ，Rusu A ，Pandele-Cuşu J ，Iordache C ，Pongratz I ，Pop MM ，Fruth V ... -  《Materials》

Resveratrol cocrystals with enhanced solubility and tabletability.

Two new 1:1 cocrystals of resveratrol (RES) with 4-aminobenzamide (RES-4ABZ) and isoniazid (RES-ISN) were synthesized by liquid assisted grinding (LAG) and rapid solvent removal (RSR) methods using ethanol as solvent. Their physiochemical properties were characterized using PXRD, DSC, solid state and solution NMR, FT-IR, and HPLC. Pharmaceutically relevant properties, including tabletability, solubility, intrinsic dissolution rate, and hygroscopicity, were evaluated. Temperature-composition phase diagram for RES-ISN cocrystal system was constructed from DSC data. Both cocrystals show higher solubility than resveratrol over a broad range of pH. They are phase stable and non-hygroscopic even under high humidity conditions. Importantly, both cocrystals exhibit improved solubility and tabletability compared with RES, which make them more suitable candidates for tablet formulation development.

Zhou Z ，Li W ，Sun WJ ，Lu T ，Tong HHY ，Sun CC ，Zheng Y ... -  《-》

Cocrystals of Praziquantel with Phenolic Acids: Discovery, Characterization, and Evaluation.

Yang S ，Liu Q ，Ji W ，An Q ，Song J ，Xing C ，Yang D ，Zhang L ，Lu Y ，Du G ... -  《MOLECULES》

Obtaining Cocrystals by Reaction Crystallization Method: Pharmaceutical Applications.

Biscaia IFB ，Gomes SN ，Bernardi LS ，Oliveira PR ... -  《Pharmaceutics》