Microsuspension of fatty acid esters of entecavir for parenteral sustained delivery
DC Field | Value | Language |
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dc.contributor.author | Ho, Myoung Jin | - |
dc.contributor.author | Lee, Dae Ro | - |
dc.contributor.author | Im, Sung Hyun | - |
dc.contributor.author | Yoon, Jeong A. | - |
dc.contributor.author | Shin, Chang Yong | - |
dc.contributor.author | Kim, Hyun Jung | - |
dc.contributor.author | Jang, Sun Woo | - |
dc.contributor.author | Choi, Young Wook | - |
dc.contributor.author | Han, Young Taek | - |
dc.contributor.author | Kang, Myung Joo | - |
dc.date.available | 2019-03-07T04:40:32Z | - |
dc.date.issued | 2018-05 | - |
dc.identifier.issn | 0378-5173 | - |
dc.identifier.issn | 1873-3476 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/2157 | - |
dc.description.abstract | Entecavir (EV), an anti-viral agent for hepatitis B infection, should be administered under fasted state, as intestinal absorption of this hydrophilic compound is markedly decreased under post-prandial conditions. Herein, in order to improve therapeutic adherence, a parenteral sustained delivery system was constructed, by synthesizing water-insoluble ester prodrugs of the nucleotide analogous with fatty acids. EV-3-palmitate (named EVP), exhibited the lowest solubility in phosphate buffered saline (pH 7.4, 1.1 mu g/ml), with extended release profile compared with EV, EV-3-myristate, and EV-3-stearate, was selected as a candidate to formulate drug suspension. The crystalline suspension was fabricated using anti-solvent crystallization technique, with a mean particle size of 7.7 mu m. After subcutaneous (SC) injection in beagle dogs (0.43 mg/kg as EV), the plasma concentrations of EV were markedly protracted with lowered maximum plasma concentration (C-max, 4.7 ng/ml), extended time required to reach C-max (T-max, 9.0 days), and lengthened elimination half-life (T-1/2,T- 129.3 h) compared with those after oral administration (0.0154 mg/kg, C-max, 15.4 ng/ml; T-max, 0.01 days; T-1/2, 4.1 h). The systemic exposure of the lipidic prodrug was below 0.1% compared with that of EV following SC injection, denoting that EV-P was rapidly converted into the parent compound in blood. Therefore, SC delivery of EV-P microsuspension can be an alternative to oral EV therapy, offering prolonged pharmacokinetic profile after single injection. | - |
dc.format.extent | 8 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | ELSEVIER SCIENCE BV | - |
dc.title | Microsuspension of fatty acid esters of entecavir for parenteral sustained delivery | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.ijpharm.2018.03.042 | - |
dc.identifier.bibliographicCitation | INTERNATIONAL JOURNAL OF PHARMACEUTICS, v.543, no.1-2, pp 52 - 59 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000432755900007 | - |
dc.identifier.scopusid | 2-s2.0-85044457094 | - |
dc.citation.endPage | 59 | - |
dc.citation.number | 1-2 | - |
dc.citation.startPage | 52 | - |
dc.citation.title | INTERNATIONAL JOURNAL OF PHARMACEUTICS | - |
dc.citation.volume | 543 | - |
dc.type.docType | Article | - |
dc.publisher.location | 네델란드 | - |
dc.subject.keywordAuthor | Entecavir | - |
dc.subject.keywordAuthor | Lipidic prodrug | - |
dc.subject.keywordAuthor | Injectable suspension | - |
dc.subject.keywordAuthor | Sustained release | - |
dc.subject.keywordAuthor | Pharmacokinetics | - |
dc.subject.keywordPlus | CHRONIC HEPATITIS-B | - |
dc.subject.keywordPlus | PALIPERIDONE PALMITATE | - |
dc.subject.keywordPlus | PHARMACOKINETICS | - |
dc.subject.keywordPlus | NANOSUSPENSIONS | - |
dc.subject.keywordPlus | SCHIZOPHRENIA | - |
dc.subject.keywordPlus | SAFETY | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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