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dc.creatorMedarević, Đorđe
dc.creatorĐuriš, Jelena
dc.creatorIbrić, Svetlana
dc.creatorMitrić, Miodrag
dc.creatorKachrimanis, Kyriakos
dc.date.accessioned2018-06-19T09:55:53Z
dc.date.available2018-06-19T09:55:53Z
dc.date.issued2018
dc.identifier.issn0378-5173
dc.identifier.urihttps://vinar.vin.bg.ac.rs/handle/123456789/7655
dc.description.abstractThe aim of this study is to develop nanosuspension of carvedilol (CRV) by wet media milling. Concentration of polymeric stabilizer (hydroxypropyl cellulose-HPC-SL), milling speed and size of milling beads were identified as critical formulation and process parameters and their effect on CRV particle size after 60 min of milling was assessed using a Box-Behnken experimental design. Optimized nanosuspension was solidified using spray drying and freeze drying and subjected to solid state characterization. Low stabilizer concentration (10%), low milling speed (300 rpm) with small milling beads (0.1 mm) were found as optimal milling conditions. Crystal lattice simulation identified potential slip plane within CRV crystals, where fractures are the most likely to occur. Calculated mechanical properties of CRV crystal indicates that low energy stress is sufficient to initiate fracture, if applied in the correct direction, explaining the advantage of using smaller milling beads. Only spray dried nanosuspension redispersed to original nanoparticles, while particle agglomeration during freeze drying prevented sample redispersion. Wet milling and spray drying did not induce polymorphic transition of CRV, while there is indication of polymorphic transition during freeze drying, making spray drying as the preferred solidification method.en
dc.relationinfo:eu-repo/grantAgreement/MESTD/Technological Development (TD or TR)/34007/RS//
dc.rightsrestrictedAccess
dc.sourceInternational Journal of Pharmaceutics
dc.subjectnanocrystalsen
dc.subjectnanosuspensionsen
dc.subjectwet media millingen
dc.subjectcrystal polymorphismen
dc.subjectexperimental designen
dc.subjectmolecular modellingen
dc.titleOptimization of formulation and process parameters for the production of carvedilol nanosuspension by wet media millingen
dc.typearticleen
dc.rights.licenseARR
dcterms.abstractМитрић, Миодраг; Кацхриманис, Кyриакос; Ибрић, Светлана; Медаревић, Ђорђе П.; Ђуриш, Јелена;
dc.rights.holder© 2018 Elsevier B.V.
dc.citation.volume540
dc.citation.issue1-2
dc.citation.spage150
dc.citation.epage161
dc.identifier.wos000427584900015
dc.identifier.doi10.1016/j.ijpharm.2018.02.011
dc.citation.rankM21
dc.identifier.pmid29438724
dc.type.versionpublishedVersion
dc.identifier.scopus2-s2.0-85042093177


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