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. 2018 May 10:277:165-172.
doi: 10.1016/j.jconrel.2018.03.018. Epub 2018 Mar 21.

In vivo evaluation of an oral self-emulsifying drug delivery system (SEDDS) for exenatide

Claudia Menzel  1 , Thomas Holzeisen  1 , Flavia Laffleur  1 , Sergey Zaichik  1 , Muthanna Abdulkarim  2 , Mark Gumbleton  2 , Andreas Bernkop-Schnürch  3
Affiliations

In vivo evaluation of an oral self-emulsifying drug delivery system (SEDDS) for exenatide

Claudia Menzel et al. J Control Release. .

Abstract

Background: The aim of the study was to develop an oral self-emulsifying drug delivery system (SEDDS) for exenatide and to evaluate its in vivo efficacy.

Methods: Exenatide was lipidised via hydrophobic ion pairing with sodium docusate (DOC) and incorporated in SEDDS consisting of 35% Cremophor EL, 25% Labrafil 1944, 30% Capmul-PG 8 and 10% propylene glycol. Exenatide/DOC was characterized in terms of lipophilicity evaluating the octanol/water phase distribution (logP). Exenatide/DOC SEDDS were characterized via droplet size analysis, drug release characteristics (log DSEDDS/release medium determination) and mucus permeation studies. Furthermore, the impact of orally administered exenatide/DOC SEDDS on blood glucose level was investigated in vivo on healthy male Sprague-Dawley rats.

Results: Hydrophobic ion pairing in a molar ratio of 1:4 (exenatide:DOC) increased the effective logP of exenatide from -1.1 to 2.1. SEDDS with a payload of 1% exenatide/DOC had a mean droplet size of 45.87 ± 2.9 nm and a Log DSEDDS/release medium of 1.9 ± 0.05. Permeation experiments revealed 2.7-fold improved mucus diffusion for exenatide/DOC SEDDS compared to exenatide in solution. Orally administered exenatide/DOC SEDDS showed a relative bioavailability (versus s.c.) of 14.62% ± 3.07% and caused a significant (p < .05) 20.6% decrease in AUC values of blood glucose levels.

Conclusion: According to these results, hydrophobic ion pairing in combination with SEDDS represents a promising tool for oral peptide delivery.

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