A new soluble and bioactive polymorph of praziquantel

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dc.cclicenceN/Aen
dc.contributor.authorZanolla, D.en
dc.contributor.authorPerissutti, Beatriceen
dc.contributor.authorPasserini, N.en
dc.contributor.authorChierotti, Michele R.en
dc.contributor.authorHasa, Dritanen
dc.contributor.authorVoinovich, Darioen
dc.contributor.authorGigli, L.en
dc.contributor.authorDemitri, N.en
dc.contributor.authorGeremia, S.en
dc.contributor.authorKeiser, J.en
dc.contributor.authorVioglio, P.C.en
dc.date.acceptance2018-01-29en
dc.date.accessioned2018-09-11T11:26:20Z
dc.date.available2018-09-11T11:26:20Z
dc.date.issued2018-01-31
dc.descriptionThe file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.en
dc.description.abstractPraziquantel is the only available drug to treat Schistosomiasis. However, its utilization is limited by many drawbacks, including the high therapeutic dose needed, resulting in large tablets and capsules difficult to be swallowed, especially from pediatric patients. In this study, an alternative option to overcome these disadvantages is proposed: to switch to a novel crystalline polymorph of racemic compound praziquantel. The preparation of the crystalline polymorph was realized via a neat grinding process in a vibrational mill. The new phase (Form B) was chemically identical to the starting material (as proved by HPLC, 1H NMR, and polarimetry), but showed different physical properties (as evaluated by SEM, differential scanning calorimetry, thermogravimetry, ATR-FTIR spectroscopy, X-ray powder diffraction, and solid-state NMR). Furthermore, the crystal structure of the new phase was solved from the powder synchrotron X-ray diffraction pattern, resulting in a monoclinic C2/c cell and validated by DFT-D calculation. Moreover the simulated solid-state NMR 13C chemical shifts were in excellent agreement with the experimental data. The conversion of original praziquantel into Form B showed to affect positively the water solubility and the intrinsic dissolution rate of praziquantel. Both the in vitro and in vivo activity against Schistosoma mansoni were maintained. Our findings suggest that the new phase, that proved to be physically stable for at least one year, is a promising product for designing a new praziquantel formulation.en
dc.funderN/Aen
dc.identifier.citationZanola, D., Parissutti, B., Passerini, N., Chierotto, M.R., Hasa, D., Voinovich, D., Gigli, L., Demitri, N., Geremia, S., Keiser, J.,Vioglio, P.C. (2018) A new soluble and bioactive polymorph of praziquantel. European Journal of Pharmaceutics and Biopharmaceutics, 127, pp. 19-28.en
dc.identifier.doihttps://doi.org/10.1016/j.ejpb.2018.01.018
dc.identifier.issn0939-6411
dc.identifier.urihttp://hdl.handle.net/2086/16567
dc.language.isoenen
dc.peerreviewedYesen
dc.projectidN/Aen
dc.publisherElsevieren
dc.researchinstituteLeicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)en
dc.subjectPraziquantelen
dc.subjectMechanochemistryen
dc.subjectSolid-state reactionsen
dc.subjectPolymorphismen
dc.subjectSolubilityen
dc.subjectBioactivityen
dc.subjectCrystal structure solutionen
dc.subjectDFT-D calculationsen
dc.subjectNeglected tropical diseasesen
dc.titleA new soluble and bioactive polymorph of praziquantelen
dc.typeArticleen

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