{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:10:54Z","timestamp":1790892654312,"version":"4.1.0"},"reference-count":29,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T00:00:00Z","timestamp":1552348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Praziquantel (PZQ) is the first line drug for the treatment of schistosome infections and is included in the WHO Model List of Essential Medicines for Children. In this study, the association of mechanochemical activation (MA) and the spray congealing (SC) technology was evaluated for developing a child-friendly PZQ dosage form, with better product handling and biopharmaceutical properties, compared to MA materials. A 1:1 by wt PZQ\u2014Povidone coground\u2014was prepared in a vibrational mill under cryogenic conditions, for favoring amorphization. PZQ was neat ground to obtain its polymorphic form (Form B), which has an improved solubility and bioactivity. Then, activated PZQ powders were loaded into microparticles (MPs) by the SC technology, using the self-emulsifying agent Gelucire\u00ae 50\/13 as a carrier. Both, the activated powders and the corresponding loaded MPs were characterized for morphology, wettability, solubility, dissolution behavior, drug content, and drug solid state (Hot Stage Microscopy (HSM), Differential Scanning Calorimetry (DSC), X-Ray Powder Diffraction Studies (PXRD), and FT-IR). Samples were also in vitro tested for a comparison with PZQ against Schistosoma mansoni newly transformed schistosomula (NTS) and adults. MPs containing both MA systems showed a further increase of biopharmaceutical properties, compared to the milled powders, while maintaining PZQ bioactivity. MPs containing PZQ Form B represented the most promising product for designing a new PZQ formulation.<\/jats:p>","DOI":"10.3390\/ijms20051233","type":"journal-article","created":{"date-parts":[[2019,3,13]],"date-time":"2019-03-13T04:07:37Z","timestamp":1552450057000},"page":"1233","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Combining Mechanochemistry and Spray Congealing for New Praziquantel Pediatric Formulations in Schistosomiasis Treatment"],"prefix":"10.3390","volume":"20","author":[{"given":"Beatrice","family":"Albertini","sequence":"first","affiliation":[{"name":"Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19\/2, 40127 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Perissutti","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Bertoni","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19\/2, 40127 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7549-7806","authenticated-orcid":false,"given":"Debora","family":"Zanolla","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Franceschinis","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, via Marzolo 5, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3830-8038","authenticated-orcid":false,"given":"Dario","family":"Voinovich","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio","family":"Lombardo","sequence":"additional","affiliation":[{"name":"Helminth Drug Development Unit, Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstr.57, CH-4051 Basel, Switzerland"},{"name":"Universit\u00e4t Basel, Petersplatz 1, P.O. Box, CH-4001 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Keiser","sequence":"additional","affiliation":[{"name":"Helminth Drug Development Unit, Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstr.57, CH-4051 Basel, Switzerland"},{"name":"Universit\u00e4t Basel, Petersplatz 1, P.O. Box, CH-4001 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Passerini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19\/2, 40127 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s40249-017-0286-2","article-title":"Controlling schistosomiasis with praziquantel: How much longer without a viable alternative?","volume":"6","author":"Bergquist","year":"2017","journal-title":"Infect. Dis. Poverty"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.actatropica.2017.08.002","article-title":"Schistosomiasis: Drugs used and treatment strategies","volume":"176","author":"Siqueira","year":"2017","journal-title":"Acta Trop."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S121","DOI":"10.1016\/j.actatropica.2010.08.020","article-title":"From innovation to application: Social-ecological context, diagnostics, drugs and integrated control of schistosomiasis","volume":"120","author":"Utzinger","year":"2011","journal-title":"Acta Trop."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1016\/S0140-6736(13)61949-2","article-title":"Human schistosomiasis","volume":"383","author":"Colley","year":"2014","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1016\/j.bmc.2017.04.031","article-title":"Medicinal chemistry of antischistosomal drugs: Praziquantel and Oxamniquine","volume":"25","author":"Campos","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"ref_6","unstructured":"WHO (2018, June 11). Available online: http:\/\/www.who.int\/medicines\/publications\/essentialmedicines\/6th_EMLc2017_FINAL_amendedAug2017.pdf?ua=1."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.ijpharm.2015.09.019","article-title":"Development of flexible and dispersible oral formulations containing praziquantel for potential schistosomiasis treatment of pre-school age children","volume":"495","author":"Trastullo","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_8","first-page":"1085","article-title":"Practical dosing of praziquantel for schistosomiasis in preschool-aged children","volume":"18","author":"Olliaro","year":"2013","journal-title":"TMIH"},{"key":"ref_9","first-page":"86","article-title":"Enhancement the oral bioavailability of praziquantel by incorporation into solid lipid nanoparticles","volume":"64","author":"Yang","year":"2009","journal-title":"Pharmazie"},{"key":"ref_10","first-page":"163","article-title":"Development and evaluation of praziquantel solid dispersions in sodium starch glycolate","volume":"12","author":"Chaud","year":"2013","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.ijpharm.2017.05.053","article-title":"An explorative analysis of process and formulation variables affecting comilling in a vibrational mill: The case of praziquantel","volume":"533","author":"Perissutti","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ejpb.2018.01.018","article-title":"A new soluble and bioactive polymorph of praziquantel","volume":"127","author":"Zanolla","year":"2018","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jpba.2018.02.018","article-title":"Milling and comilling Praziquantel at cryogenic and room temperatures: Assessment of the process-induced effects on drug properties","volume":"153","author":"Zanolla","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_14","unstructured":"(2019, March 06). EMA Guideline on Pharmaceutical Development of Medicines for Paediatric Use. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-pharmaceutical-development-medicines-paediatric-use_en.pdf."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.phymed.2011.06.027","article-title":"A new approach to enhance oral bioavailability of Silybum Marianum dry extract: Association of mechanochemical activation and spray congealing","volume":"19","author":"Passerini","year":"2012","journal-title":"Phytomed"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3109\/02652048.2014.985341","article-title":"Formulation of spray congealed microparticles with self-emulsifying ability for enhanced glibenclamide dissolution performance","volume":"32","author":"Albertini","year":"2015","journal-title":"J. Microencapsul."},{"key":"ref_17","first-page":"479","article-title":"Solid dispersions of carbamazepine with Gelucire 44\/14 and 50\/13","volume":"10","author":"Perissutti","year":"2000","journal-title":"S.T.P. Pharma Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ijpharm.2014.04.055","article-title":"Formulating SLMs as oral pulsatile system for potential delivery of melatonin to pediatric population","volume":"469","author":"Albertini","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1002\/jps.21832","article-title":"An investigation into the mechanism of dissolution rate enhancement of poorly water-soluble drugs from spray chilled gelucire 50\/13 microspheres","volume":"99","author":"Qi","year":"2010","journal-title":"J. Pharm. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.jpba.2018.07.002","article-title":"Identification of degradation products of praziquantel during the mechanochemical activation","volume":"159","author":"Zanolla","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ejps.2013.03.018","article-title":"Reduction of melting temperature and enthalpy of drug crystals: Theoretical aspects","volume":"50","author":"Hasa","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s00894-017-3266-3","article-title":"Molecular modeling and infrared and Raman spectroscopy of the crystal structure of the chiral antiparasitic drug Praziquantel","volume":"23","year":"2017","journal-title":"J. Mol. Model."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1021\/cg301314w","article-title":"Cocrystals of Active Pharmaceutical Ingredients\u2014Praziquantel in Combination with Oxalic, Malonic, Succinic, Maleic, Fumaric, Glutaric, Adipic, And Pimelic Acids","volume":"13","year":"2013","journal-title":"Cryst. Growth Des."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/j.ijpharm.2016.08.009","article-title":"Unexpected solvent impact in the crystallinity of praziquantel\/poly (vinylpyrrolidone) formulations. A solubility, DSC and solid-state NMR study","volume":"511","author":"Costa","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17721","DOI":"10.1021\/jp047989m","article-title":"Structural and thermal characterization of mono- and diacyl polyoxyethylene glycol by infrared spectroscopy and X-ray diffraction coupled to differential calorimetry","volume":"108","author":"Brubach","year":"2004","journal-title":"J. Phys. Chem. B"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.jchromb.2012.05.004","article-title":"Simple, cheap and effective high-performance liquid chromatographic method for determination of praziquantel in bovine muscle","volume":"899","author":"Sun","year":"2012","journal-title":"J. Chromatogr. B"},{"key":"ref_27","unstructured":"(2014). Praziquantel. European Pharmacopoeia 8.0, Directorate for the Quality of Medicines of the Council of Europe (EDQM)."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1248\/cpb.58.230","article-title":"Enhancement of wettability and dissolution properties of cilostazol using the supercritical antisolvent process: Effect of various additives","volume":"58","author":"Kim","year":"2010","journal-title":"Chem. Pharm. Bull."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/s41596-018-0101-y","article-title":"Life cycle maintenance and drug-sensitivity assays for early drug discovery in Schistosoma mansoni","volume":"14","author":"Lombardo","year":"2019","journal-title":"Nat. Protoc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/5\/1233\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:38:03Z","timestamp":1760186283000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/5\/1233"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,12]]},"references-count":29,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,3]]}},"alternative-id":["ijms20051233"],"URL":"https:\/\/doi.org\/10.3390\/ijms20051233","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,12]]}}}