Mechanochemical Synthesis and Physicochemical Characterization of Previously Unreported Praziquantel Solvates with 2-Pyrrolidone and Acetic Acid.
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Zanolla, D., Gigli, L., Hasa, D., Chierotti, M. R., Arhangelskis, M., Demitri, N., Jones, W., et al. (2021). Mechanochemical Synthesis and Physicochemical Characterization of Previously Unreported Praziquantel Solvates with 2-Pyrrolidone and Acetic Acid.. Pharmaceutics, 13 (10) https://doi.org/10.3390/pharmaceutics13101606
Two new solvates of the widely used anthelminthic Praziquantel (PZQ) were obtained through mechanochemical screening with different liquid additives. Specifically, 2-pyrrolidone and acetic acid gave solvates with 1:1 stoichiometry (PZQ-AA and PZQ-2P, respectively). A wide-ranging characterization of the new solid forms was carried out by means of powder X-ray diffraction, differential scanning calorimetry, FT-IR, solid-state NMR and biopharmaceutical analyses (solubility and intrinsic dissolution studies). Besides, the crystal structures of the two new solvates were solved from their Synchrotron-PXRD pattern: the solvates are isostructural, with equivalent triclinic packing. In both structures acetic acid and 2-pyrrolidone showed a strong interaction with the PZQ molecule via hydrogen bond. Even though previous studies have shown that PZQ is conformationally flexible, the same <i>syn</i> conformation as the PZQ Form A of the C=O groups of the piperazinone-cyclohexylcarbonyl segment is involved in these two new solid forms. In terms of biopharmaceutical properties, PZQ-AA and PZQ-2P exhibited water solubility and intrinsic dissolution rate much greater than those of anhydrous Form A.
Acetic acid, praziquantel, Solvates, Mechanochemistry, 2-Pyrrolidone, Liquid-assisted Grinding
National Science Center Poland (2018/31/D/ST5/03619)
External DOI: https://doi.org/10.3390/pharmaceutics13101606
This record's URL: https://www.repository.cam.ac.uk/handle/1810/332165
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/