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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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Autores principales: Zanolla, Debora, Gigli, Lara, Hasa, Dritan, Chierotti, Michele R., Arhangelskis, Mihails, Demitri, Nicola, Jones, William, Voinovich, Dario, Perissutti, Beatrice
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540171/
https://www.ncbi.nlm.nih.gov/pubmed/34683899
http://dx.doi.org/10.3390/pharmaceutics13101606
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author Zanolla, Debora
Gigli, Lara
Hasa, Dritan
Chierotti, Michele R.
Arhangelskis, Mihails
Demitri, Nicola
Jones, William
Voinovich, Dario
Perissutti, Beatrice
author_facet Zanolla, Debora
Gigli, Lara
Hasa, Dritan
Chierotti, Michele R.
Arhangelskis, Mihails
Demitri, Nicola
Jones, William
Voinovich, Dario
Perissutti, Beatrice
author_sort Zanolla, Debora
collection PubMed
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 syn 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.
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spelling pubmed-85401712021-10-24 Mechanochemical Synthesis and Physicochemical Characterization of Previously Unreported Praziquantel Solvates with 2-Pyrrolidone and Acetic Acid Zanolla, Debora Gigli, Lara Hasa, Dritan Chierotti, Michele R. Arhangelskis, Mihails Demitri, Nicola Jones, William Voinovich, Dario Perissutti, Beatrice Pharmaceutics Article 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 syn 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. MDPI 2021-10-02 /pmc/articles/PMC8540171/ /pubmed/34683899 http://dx.doi.org/10.3390/pharmaceutics13101606 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zanolla, Debora
Gigli, Lara
Hasa, Dritan
Chierotti, Michele R.
Arhangelskis, Mihails
Demitri, Nicola
Jones, William
Voinovich, Dario
Perissutti, Beatrice
Mechanochemical Synthesis and Physicochemical Characterization of Previously Unreported Praziquantel Solvates with 2-Pyrrolidone and Acetic Acid
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540171/
https://www.ncbi.nlm.nih.gov/pubmed/34683899
http://dx.doi.org/10.3390/pharmaceutics13101606
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