Mechanochemical Synthesis of New Praziquantel Cocrystals

New cocrystals of praziquantel with suberic, 3-hydroxybenzoic, benzene-1,2,4,5-tetracarboxylic, trimesic, and 5-hydroxyisophthalic acids were obtained through ball milling experiments. The optimal conditions for the milling process were chosen by changing the solvent volume and the mechanical action time. Supramolecular interactions in the new cocrystals are detailed based on single-crystal X-ray diffraction analysis, confirming the expected formation of hydrogen bonds between the praziquantel carbonyl group and the carboxyl (or hydroxyl) moieties of the coformers. Different structural characterization techniques were performed for all samples, but the praziquantel:suberic acid cocrystal includes a wider range of investigations such as thermal analysis, infrared and X-ray photoelectron spectroscopies, and SEM microscopy. The stability for up to five months was established by keeping it under extreme conditions of temperature and humidity. Solubility studies were carried out for all the new forms disclosed herein and compared with the promising cocrystals previously reported with salicylic, 4-aminosalicylic, vanillic, and oxalic acids. HPLC analyses revealed a higher solubility for most of the new cocrystal forms, as compared to pure praziquantel.

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The authors acknowledge Fundac\u0327a\u0303o para a Cie\u0302ncia e a Tecnologia, and FEDER, Portugal 2020, and Lisboa 2020 for funding (project LISBOA-01-0145-FEDER-030988). Financial support is also acknowledged from grant POWR.03.02.00-00-I026/16 co-financed by the European Union through the European Social Fund under the Operational Program Knowledge Education Development and from Adam Mickiewicz University for the funds from the Initiative of Excellence Research University (ID-UB) program.This work is a contribution to the COST Action CA18112-Mechanochemistry for Sustainable Industry. Publisher Copyright: © 2024 The Authors. Published by American Chemical Society.