Mechanochemical Synthesis and Physicochemical Characterization of Previously Unreported Praziquantel Solvates with 2-Pyrrolidone and Acetic Acid.
cam.issuedOnline | 2021-10-02 | |
dc.contributor.author | Zanolla, Debora | |
dc.contributor.author | Gigli, Lara | |
dc.contributor.author | Hasa, Dritan | |
dc.contributor.author | Chierotti, Michele R | |
dc.contributor.author | Arhangelskis, Mihails | |
dc.contributor.author | Demitri, Nicola | |
dc.contributor.author | Jones, William | |
dc.contributor.author | Voinovich, Dario | |
dc.contributor.author | Perissutti, Beatrice | |
dc.contributor.orcid | Zanolla, Debora [0000-0001-7549-7806] | |
dc.contributor.orcid | Gigli, Lara [0000-0002-7787-5804] | |
dc.contributor.orcid | Chierotti, Michele R [0000-0002-8734-6009] | |
dc.contributor.orcid | Arhangelskis, Mihails [0000-0003-1150-3108] | |
dc.contributor.orcid | Demitri, Nicola [0000-0003-0288-3233] | |
dc.contributor.orcid | Voinovich, Dario [0000-0003-3830-8038] | |
dc.contributor.orcid | Perissutti, Beatrice [0000-0002-5766-4014] | |
dc.date.accessioned | 2022-01-06T11:51:14Z | |
dc.date.available | 2022-01-06T11:51:14Z | |
dc.date.issued | 2021-10-02 | |
dc.date.updated | 2022-01-06T11:51:13Z | |
dc.description.abstract | 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. | |
dc.identifier.doi | 10.17863/CAM.79611 | |
dc.identifier.eissn | 1999-4923 | |
dc.identifier.issn | 1999-4923 | |
dc.identifier.other | PMC8540171 | |
dc.identifier.other | 34683899 | |
dc.identifier.uri | https://www.repository.cam.ac.uk/handle/1810/332165 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | MDPI AG | |
dc.publisher.url | http://dx.doi.org/10.3390/pharmaceutics13101606 | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.source | essn: 1999-4923 | |
dc.source | nlmid: 101534003 | |
dc.subject | 2-pyrrolidone | |
dc.subject | acetic acid | |
dc.subject | liquid-assisted grinding | |
dc.subject | mechanochemistry | |
dc.subject | praziquantel | |
dc.subject | solvates | |
dc.title | Mechanochemical Synthesis and Physicochemical Characterization of Previously Unreported Praziquantel Solvates with 2-Pyrrolidone and Acetic Acid. | |
dc.type | Article | |
dcterms.dateAccepted | 2021-09-28 | |
prism.issueIdentifier | 10 | |
prism.publicationName | Pharmaceutics | |
prism.volume | 13 | |
pubs.funder-project-id | National Science Center Poland (2018/31/D/ST5/03619) | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0/ | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.3390/pharmaceutics13101606 |
Files
Original bundle
1 - 1 of 1
Loading...
- Name:
- article.pdf
- Size:
- 4.83 MB
- Format:
- Adobe Portable Document Format
- Description:
- Published version
- Licence
- https://creativecommons.org/licenses/by/4.0/