Next Article in Journal
Nanogel: A Versatile Nano-Delivery System for Biomedical Applications
Previous Article in Journal
Nanostructured Lipid Carriers for Delivery of Chemotherapeutics: A Review
Previous Article in Special Issue
The Polymorphism of Drugs: New Approaches to the Synthesis of Nanostructured Polymorphs
Open AccessArticle

Mechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties

1
Department of Chemical and Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste, Italy
2
Faculty of Chemistry, University of Warsaw, 1 Pasteura Street, 02-093 Warsaw, Poland
3
Department of Chemistry, University of Cambridge, Lensfield Road, CB2-1EW Cambridge, UK
4
Department of Chemistry and NIS Centre, University of Torino, V. Giuria 7, 10125 Torino, Italy
5
Swiss Tropical and Public Health Institute, Socinstrasse 57, P.O. Box, CH-4002 Basel; Switzerland
6
Universität Basel, Petersplatz 1, P.O. Box, CH-4001 Basel, Switzerland
*
Authors to whom correspondence should be addressed.
Current Affiliation: Programme of Pharmacy, Federal University of Santa Catarina, Florianopolis 88040-900, Brazil.
Pharmaceutics 2020, 12(3), 289; https://doi.org/10.3390/pharmaceutics12030289
Received: 4 March 2020 / Revised: 19 March 2020 / Accepted: 20 March 2020 / Published: 23 March 2020
(This article belongs to the Special Issue Drug Polymorphism and Dosage Form Design)
Praziquantel (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. View Full-Text
Keywords: praziquantel; hemihydrate; mechanochemistry; neat grinding; liquid-assisted grinding; racemic compound; polymorphism; crystal structure solution praziquantel; hemihydrate; mechanochemistry; neat grinding; liquid-assisted grinding; racemic compound; polymorphism; crystal structure solution
Show Figures

Graphical abstract

  • Supplementary File 1:

    ZIP-Document (ZIP, 2402 KB)

  • Externally hosted supplementary file 1
    Link: http://www.ccdc.cam.ac.uk/structures
    Description: CCDC 1530464 contains the supplementary crystallographic data for racemic praziquantel hemihydrate (PZQ-HH)
MDPI and ACS Style

Zanolla, D.; Hasa, D.; Arhangelskis, M.; Schneider-Rauber, G.; Chierotti, M.R.; Keiser, J.; Voinovich, D.; Jones, W.; Perissutti, B. Mechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties. Pharmaceutics 2020, 12, 289.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop