International Journal of Pharmaceutics 2014-12-30

Self-nanoemulsifying drug delivery systems for oral insulin delivery: in vitro and in vivo evaluations of enteric coating and drug loading.

Ping Li, Angel Tan, Clive A Prestidge, Hanne Mørck Nielsen, Anette Müllertz

Index: Int. J. Pharm. 477(1-2) , 390-8, (2014)

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Abstract

This study aims at evaluating the combination of self-nanoemulsifying drug delivery systems (SNEDDS) and enteric-coated capsules as a potential delivery strategy for oral delivery of insulin. The SNEDDS preconcentrates, loaded with insulin-phospholipid complex at different levels (0, 2.5 and 10% w/w), were readily dispersed in water to form nanoemulsions of 35 nm and vesicles of 300 nm. The association efficiency of non-complexed insulin in the dispersed SNEDDS was 18.6%, and was increased to 73.1% for insulin-phospholipid complex (at 10% loading level). The morphology of the dispersed SNEDDS changed from nanoemulsion droplets to vesicular structures with increasing complex loading levels. A pH-dependent insulin release profile was observed for SNEDDS filled into capsules coated with the enteric polymer, Eudragit(®) L100. Using a Caco-2 cell model, it was observed that the transport of insulin was enhanced by factors of 7.7- and 9.3- for SNEDDS loaded with 2.5 and 10% complex, respectively. In healthy fasted rats, administration of SNEDDS (10% complex) filled in enteric-coated capsules produced a 2.7-fold and 3.4-fold enhancement in the relative bioavailability and glucose reduction, respectively. This study shows the effectiveness of combining SNEDDS (loaded with insulin-phospholipid complex) with enteric-coated capsules for enhancing the oral absorption and efficacy of insulin.Copyright © 2014 Elsevier B.V. All rights reserved.