Development, in vitro and in vivo evaluation of a self-emulsifying drug delivery system (SEDDS) for oral enoxaparin administration

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• 作者：Ožbej Zupančič^a ; Julia Anita Grieβinger^b ; Julia Rohrer^a ; Irene Pereira de Sousa^a ; Lukas Danninger^a ; Alexandra Partenhauser^a ; Nadine Elli Sü ; ndermann^c ; Flavia Laffleur^a ; Andreas Bernkop-Schnü ; rch^a ; ^{andreas.bernkop@uibk.ac.at}
• 关键词：Hydrophobic ion pairing ; Oral LMWH delivery ; Self-emulsifying drug delivery systems (SEDDS)
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：109
• 期：Complete
• 页码：113-121
• 全文大小：536 K
• 卷排序：109

文摘

The aim of this study was to develop SEDDS for oral enoxaparin administration and evaluate it in vitro and in vivo.MethodsThe emulsifying properties of SEDDS composed of long chain lipids (LC-SEDDS), medium chain lipids (MC-SEDDS), short chain lipids (SC-SEDDS) and no lipids (NL-SEDDS) were evaluated. Thereafter, enoxaparin was incorporated via hydrophobic ion pairing in the chosen SEDDS, which were evaluated regarding their mucus permeating properties, stability towards pancreatic lipase, drug release profile and cytotoxicity. Finally, in vivo performance of SEDDS was evaluated.ResultsThe average droplet size of chosen LC-SEDDS, MC-SEDDS and NL-SEDDS ranged between 30 and 40 nm. MC-SEEDS containing 30% Captex 8000, 30% Capmul MCM, 30% Cremophor EL and 10% propylene glycol and NL-SEDDS containing 31.5% Labrafil 1944, 22.5% Capmul PG-8, 9% propylene glycol, 27% Cremophor EL and 10% DMSO exhibited 2-fold higher mucus diffusion than LC-SEDDS and were therefore chosen for further studies. The enoxaparin-dodecylamine complex (ENOX/DOA) was incorporated in a payload of 2% (w/w) into MC-SEDDS and NL-SEDDS. After 90 min 97% of MC-SEDDS and 5% of NL-SEDDS were degraded by pancreatic lipase. Both MC-SEDDS and NL-SEDDS showed sustained in vitro enoxaparin release. Furthermore, orally administrated MC-SEDDS and NL-SEDDS yielded an absolute enoxaparin bioavailability of 2.02% and 2.25%, respectively.ConclusionAccording to the abovementioned findings, SEDDS could be considered as a potential oral LMWH delivery system.