1 Biologics, Department of Pharmacy, Faculty of Health and Medical Sciences, Københavns Universitet2 Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, Københavns Universitet3 IKVH Fysiologi og ernæring samt pelsdyrfarmen, Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, Københavns Universitet4 Drug Research Academy A, Drug Research Academy, Faculty of Pharmaceutical Sciences, Københavns Universitet5 unknown6 Drug Research Academy A, Drug Research Academy, Faculty of Pharmaceutical Sciences, Københavns Universitet7 Biologics, Department of Pharmacy, Faculty of Health and Medical Sciences, Københavns Universitet8 Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, Københavns Universitet
In vitro and in vivo evaluations of enteric coating and drug loading
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 35nm and vesicles of 300nm. 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.
International Journal of Pharmaceutics, 2014, Vol 477, Issue 1-2, p. 390-8