Show simple item record

dc.creatorCetković, Zora
dc.creatorCvijić, Sandra
dc.creatorVasiljević, Dragana
dc.date.accessioned2019-09-02T12:06:55Z
dc.date.available2019-09-02T12:06:55Z
dc.date.issued2018
dc.identifier.issn0363-9045
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/3178
dc.description.abstractObjective: The aims of this study were to formulate simvastatin (SV)-loaded self-microemulsifying drug delivery systems (SMEDDS), and explore the potential of these drug delivery systems to improve SV solubility, and also to identify the optimal place in the gastrointestinal (GI) tract for the release of SV using coupled in vitro/in silico approach. Significance: In comparison to other published results, this study considered the extensive pre-systemic clearance of SV, which could significantly decrease its systemic and hepatic bioavailability if SV is delivered into the small intestine. Methods: SV-loaded SMEDDS were formulated using various proportions of oils (PEG 300 oleic glycerides, propylene glycol monocaprylate, propylene glycol monolaurate), surfactant (PEG 400 caprylic/capric glycerides) and cosurfactant (polysorbate 80) and subjected to characterization, and physiologically-based pharmacokinetic (PBPK) modeling. Results: According to the in vitro results, the selected SMEDDS consisted of 10.0% PEG 300 oleic glycerides, 67.5% PEG 400 caprylic/capric glycerides, and 22.5% polysorbate 80. The use of acid-resistant capsules filled with SV-loaded SMEDDS was found helpful in protecting the drug against early degradation in proximal parts of the GI tract, however, in silico simulations indicated that pH-controlled drug release system that dissolve in the distal parts of the intestine might further improve SV bioavailability (up to 7.20%). Conclusion: The obtained results suggested that combined strategy for the improvement of SV bioavailability should comprise solubility enhancement and delayed drug release. The developed SV-specific PBPK model could potentially be used to assess the influence of formulation factors on drug absorption and disposition when developing SV oral dosage forms.en
dc.publisherTaylor & Francis Ltd, Abingdon
dc.relationinfo:eu-repo/grantAgreement/MESTD/Technological Development (TD or TR)/34007/RS//
dc.rightsrestrictedAccess
dc.sourceDrug Development and Industrial Pharmacy
dc.subjectSelf-microemulsifying drug delivery systems (SMEDDS)en
dc.subjectsimvastatinen
dc.subjectpoor solubilityen
dc.subjectabsorption simulationen
dc.subjectphysiologically-based pharmacokinetic modelingen
dc.titleIn vitro/in silico approach in the development of simvastatin-loaded self-microemulsifying drug delivery systemsen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractЦвијић, Сандра; Васиљевић, Драгана; Цетковић, Зора;
dc.citation.volume44
dc.citation.issue5
dc.citation.spage849
dc.citation.epage860
dc.citation.other44(5): 849-860
dc.citation.rankM22
dc.description.otherPeer-reviewed manuscript: [http://farfar.pharmacy.bg.ac.rs/handle/123456789/3430]
dc.identifier.wos000426910800017
dc.identifier.doi10.1080/03639045.2017.1414835
dc.identifier.pmid29228833
dc.identifier.scopus2-s2.0-85038388404
dc.identifier.rcubconv_4069
dc.type.versionpublishedVersion


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record