In vivo evaluation of an oral self-emulsifying drug delivery system (SEDDS) for exenatide.
J Control Release
; 277: 165-172, 2018 05 10.
Article
em En
| MEDLINE
| ID: mdl-29574041
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 14 (exenatideDOC) 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⯱â¯2.9â¯nm and a Log DSEDDS/release medium of 1.9⯱â¯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%⯱â¯3.07% and caused a significant (pâ¯<â¯.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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Sistemas de Liberação de Medicamentos
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Emulsificantes
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Exenatida
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article