Preparation and characterization of self nano-emulsifying drug delivery system (SNEDDS) for oral delivery of heparin using hydrophobic complexation by cationic polymer of β-cyclodextrin.

OBJECTIVE: The aim of this study was the preparation of a self nano-emulsifying drug delivery system (SNEDDS) for oral delivery of heparin.

SIGNIFICANCE: Preparation of hydrophobic complexes between heparin as the hydrophilic macromolecule and cationic polymer of β-cyclodextrin (CPβCD) was considered for preparation of orally administered SNEDDS in which the drug incorporated in internal oil phase of O/W nano-droplets.

METHODS: Hydrophobic complexes of heparin-CPβCD were prepared by electrostatic interaction. The lipophilic feature of complexes was characterized by determining their partition co-efficients. SNEDDS prototypes were prepared by mixing liquid paraffin, Tween 80, propylene glycol and ethanol, diluted 1:100 in an aqueous medium. Central composite response surface methodology was applied for statistical optimization. Independent variables were the amount of liquid paraffin and the amount of Tween 80, while responses were size and poly dispersity index (PdI). Optimized SNEDDS were studied morphologically using transmission electron microscopy (TEM). In vitro release of heparin was studied in the simulated gastric and simulated intestinal media.

RESULTS: The data revealed that in molar ratio 1:3 (heparin:CPβCD), the n-octanol recovery was maximized and reached 67.6 ± 11.86%. Size, PdI, zeta potential, EE% in gastric medium and EE% in intestinal medium for optimized nano-droplets were reported as 307 ± 30.51 nm, 0.236 ± 0.02, +2.1 ± 0.66 mV, 90.2 ± 0.04 and 96.1 ± 0.73%, respectively. Microscopic images revealed spherical nano-droplets. The obtained data revealed no burst release of heparin from nano-droplets.

CONCLUSIONS: The obtained results indicate that SNEDDS could be regarded as a good candidate for oral delivery of heparin as the hydrophilic macromolecule.