Mechanochemical Synthesis and Physicochemical Characterization of Previously Unreported Praziquantel Solvates with 2-Pyrrolidone and Acetic Acid
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...
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MDPI AG
2021-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/10/1606 |
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| author | Debora Zanolla Lara Gigli Dritan Hasa Michele R. Chierotti Mihails Arhangelskis Nicola Demitri William Jones Dario Voinovich Beatrice Perissutti |
| author_facet | Debora Zanolla Lara Gigli Dritan Hasa Michele R. Chierotti Mihails Arhangelskis Nicola Demitri William Jones Dario Voinovich Beatrice Perissutti |
| author_sort | Debora Zanolla |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T06:16:16Z |
| format | Article |
| id | doaj.art-6c0ceb62ec4f477ab8dd529862674398 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T06:16:16Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-6c0ceb62ec4f477ab8dd5298626743982023-11-22T19:38:24ZengMDPI AGPharmaceutics1999-49232021-10-011310160610.3390/pharmaceutics13101606Mechanochemical Synthesis and Physicochemical Characterization of Previously Unreported Praziquantel Solvates with 2-Pyrrolidone and Acetic AcidDebora Zanolla0Lara Gigli1Dritan Hasa2Michele R. Chierotti3Mihails Arhangelskis4Nicola Demitri5William Jones6Dario Voinovich7Beatrice Perissutti8Department of Chemical and Pharmaceutical Sciences, University of Trieste, Piazzale Europa 1, 34127 Trieste, ItalyElettra-Sincrotrone Trieste, S.S. 14 Km 163.5, Area Science Park, Basovizza, 34149 Trieste, ItalyDepartment of Chemical and Pharmaceutical Sciences, University of Trieste, Piazzale Europa 1, 34127 Trieste, ItalyDepartment of Chemistry and NIS Centre, University of Torino, V. Giuria 7, 10125 Torino, ItalyFaculty of Chemistry, University of Warsaw 1 Pasteura Street, 02-093 Warsaw, PolandElettra-Sincrotrone Trieste, S.S. 14 Km 163.5, Area Science Park, Basovizza, 34149 Trieste, ItalyDepartment of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UKDepartment of Chemical and Pharmaceutical Sciences, University of Trieste, Piazzale Europa 1, 34127 Trieste, ItalyDepartment of Chemical and Pharmaceutical Sciences, University of Trieste, Piazzale Europa 1, 34127 Trieste, ItalyTwo 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.https://www.mdpi.com/1999-4923/13/10/1606praziquantelsolvatesacetic acid2-pyrrolidonemechanochemistryliquid-assisted grinding |
| spellingShingle | Debora Zanolla Lara Gigli Dritan Hasa Michele R. Chierotti Mihails Arhangelskis Nicola Demitri William Jones Dario Voinovich Beatrice Perissutti Mechanochemical Synthesis and Physicochemical Characterization of Previously Unreported Praziquantel Solvates with 2-Pyrrolidone and Acetic Acid Pharmaceutics praziquantel solvates acetic acid 2-pyrrolidone mechanochemistry liquid-assisted grinding |
| title | Mechanochemical Synthesis and Physicochemical Characterization of Previously Unreported Praziquantel Solvates with 2-Pyrrolidone and Acetic Acid |
| title_full | Mechanochemical Synthesis and Physicochemical Characterization of Previously Unreported Praziquantel Solvates with 2-Pyrrolidone and Acetic Acid |
| title_fullStr | Mechanochemical Synthesis and Physicochemical Characterization of Previously Unreported Praziquantel Solvates with 2-Pyrrolidone and Acetic Acid |
| title_full_unstemmed | Mechanochemical Synthesis and Physicochemical Characterization of Previously Unreported Praziquantel Solvates with 2-Pyrrolidone and Acetic Acid |
| title_short | Mechanochemical Synthesis and Physicochemical Characterization of Previously Unreported Praziquantel Solvates with 2-Pyrrolidone and Acetic Acid |
| title_sort | mechanochemical synthesis and physicochemical characterization of previously unreported praziquantel solvates with 2 pyrrolidone and acetic acid |
| topic | praziquantel solvates acetic acid 2-pyrrolidone mechanochemistry liquid-assisted grinding |
| url | https://www.mdpi.com/1999-4923/13/10/1606 |
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