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dc.creatorMedarević, Đorđe
dc.creatorCvijić, Sandra
dc.creatorDobričić, Vladimir
dc.creatorMitrić, Miodrag
dc.creatorĐuriš, Jelena
dc.creatorIbrić, Svetlana
dc.date.accessioned2019-09-02T12:03:25Z
dc.date.available2019-09-02T12:03:25Z
dc.date.issued2018
dc.identifier.issn0928-0987
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/3045
dc.description.abstractThis study aimed to improve dissolution rate of valsartan in an acidic environment and consequently its oral bioavailability by solid dispersion formulation. Valsartan was selected as a model drug due to its low oral bioavailability (similar to 23%) caused by poor solubility of this drug in the low pH region of gastrointestinal tract (GIT) and presence of absorption window in the upper part of GIT. Solid dispersions were prepared by solvent evaporation method with Eudragit (R) E100, Soluplus (R) or polyvinylpyrrolidone K25 (PVP K25) in drug:polymer weight ratios of 1:1, 1:2, 1:4 and 1:6 and further subjected to solid-state characterization and in vitro drug dissolution testing in 0.1 M HCl. The expected drug plasma concentration vs. time profiles after oral administration of the selected solid dispersion formulations were predicted using physiologically-based in silico modeling. Fast and complete dissolution of valsartan, with > 80% of dissolved drug within the first 10 min of testing, was observed only from solid dispersions prepared with Eudragit (R) E100 in drug:polymer ratios of 1:2, 1:4 and 1:6. In all other samples, valsartan dissolution was slow and incomplete. Solid-state characterization showed amorphous nature of both pure drug and solid dispersion samples, as well as favourable intermolecular interactions between valsartan and polymers over interactions between drug molecules. The constructed in silico model predicted > 40% of increase in valsartan bioavailability, C-max and AUC values from selected solid dispersion formulations compared to conventional solid oral dosage form such as IR capsules. Based on the results of the in vitro-in silico study, formulation of solid dispersions of valsartan with Eudragit (R) E100 polymer can be considered as a promising approach for improving valsartan bioavailability.en
dc.publisherElsevier Science BV, Amsterdam
dc.relationinfo:eu-repo/grantAgreement/MESTD/Technological Development (TD or TR)/34007/RS//
dc.rightsrestrictedAccess
dc.sourceEuropean Journal of Pharmaceutical Sciences
dc.subjectSolid dispersionsen
dc.subjectPoorly soluble drugsen
dc.subjectBioavailabilityen
dc.subjectin silico modelingen
dc.titleAssessing the potential of solid dispersions to improve dissolution rate and bioavailability of valsartan: In vitro-in silico approachen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractМедаревић, Ђорђе; Митрић, Миодраг; Ибрић, Светлана; Добричић, Владимир; Ђуриш, Јелена; Цвијић, Сандра;
dc.citation.volume124
dc.citation.spage188
dc.citation.epage198
dc.citation.other124: 188-198
dc.citation.rankM21
dc.identifier.wos000447981200019
dc.identifier.doi10.1016/j.ejps.2018.08.026
dc.identifier.pmid30144529
dc.identifier.scopus2-s2.0-85052733090
dc.identifier.rcubconv_4237
dc.type.versionpublishedVersion


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