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

Abstract

Aim: The aim of this study was to develop SEDDS for oral enoxaparin administration and evaluate it in vitro and in vivo.

Methods: The 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.

Results: The average droplet size of chosen LC-SEDDS, MC-SEDDS and NL-SEDDS ranged between 30 and 40nm. 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 90min 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.

Conclusion: According to the abovementioned findings, SEDDS could be considered as a potential oral LMWH delivery system.

Keywords: Hydrophobic ion pairing; Oral LMWH delivery; Self-emulsifying drug delivery systems (SEDDS).