Show simple item record

dc.contributor.authorZanolla, Debora
dc.contributor.authorHasa, Dritan
dc.contributor.authorArhangelskis, Mihails
dc.contributor.authorSchneider-Rauber, Gabriela
dc.contributor.authorChierotti, Michele R.
dc.contributor.authorKeiser, Jennifer
dc.contributor.authorVoinovich, Dario
dc.contributor.authorJones, William
dc.contributor.authorPerissutti, Beatrice
dc.date.accessioned2020-03-26T03:11:31Z
dc.date.available2020-03-26T03:11:31Z
dc.date.issued2020-03-23
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/303784
dc.description.abstractPraziquantel (PZQ) is the first-line drug used against schistosomiasis, one of the most common parasitic diseases in the world. A series of crystalline structures including two new polymorphs of the pure drug and a series of cocrystals of PZQ have been discovered and deposited in the Cambridge Structural Database (CSD). This work adds to the list of multicomponent forms of PZQ a relevant example of a racemic hemihydrate (PZQ-HH), obtainable from commercial PZQ (polymorphic Form A) through mechanochemistry. Noteworthy, the formation of the new hemihydrate strongly depends on the initial polymorphic form of PZQ and on the experimental conditions used. The new PZQ-HH has been fully characterized by means of HPLC, Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Hot-Stage Microscopy (SEM), Powder X-Ray Diffraction (PXRD), Scanning Electron Microscopy (SEM), FT-IR, polarimetry, solid-state NMR (SS-NMR), solubility and intrinsic dissolution rate (IDR), and in vitro tests on Schistosoma mansoni adults. The crystal structure was solved from the powder X-ray diffraction pattern and validated by periodic-DFT calculations. The new bioactive hemihydrate was physically stable for three months and showed peculiar biopharmaceutical features including enhanced solubility and a double intrinsic dissolution rate in water in comparison to the commercially available PZQ Form A.
dc.languageen
dc.publisherMDPI
dc.subjectpraziquantel
dc.subjecthemihydrate
dc.subjectmechanochemistry
dc.subjectneat grinding
dc.subjectliquid-assisted grinding
dc.subjectracemic compound
dc.subjectpolymorphism
dc.subjectcrystal structure solution
dc.titleMechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties
dc.typeArticle
dc.date.updated2020-03-26T03:11:31Z
prism.issueIdentifier3
prism.publicationNamePharmaceutics
prism.volume12
dc.identifier.doi10.17863/CAM.50863
dcterms.dateAccepted2020-03-20
rioxxterms.versionofrecord10.3390/pharmaceutics12030289
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidZanolla, Debora [0000-0001-7549-7806]
dc.contributor.orcidHasa, Dritan [0000-0003-2147-9121]
dc.contributor.orcidArhangelskis, Mihails [0000-0003-1150-3108]
dc.contributor.orcidChierotti, Michele R. [0000-0002-8734-6009]
dc.contributor.orcidKeiser, Jennifer [0000-0003-0290-3521]
dc.contributor.orcidVoinovich, Dario [0000-0003-3830-8038]
dc.contributor.orcidPerissutti, Beatrice [0000-0002-5766-4014]
dc.identifier.eissn1999-4923


Files in this item

Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record