Development, optimization and in vitro evaluation of norcantharidin loadedself-nanoemulsifying drug delivery systems (NCTD-SNEDDS)

Abstract

This study focused on developing a self-nanoemulsifying drug delivery system (SNEDDS) containing bioactive surfactants under an efficient screening approach for overcoming problems associated with the delivery of norcantharidin (NCTD), a high dose chemotherapy agent having pH dependent solubility. Preliminary screening was implemented to select proper components combination. Besides the solubility of NCTD in the oil phase, emulsifying efficiency, droplet size and size distribution were also employed to select components of the SNEDDS. Moreover, the influence of surfactant and co-surfactant on the interfacial tension and droplets of nanoemulsions were investigated to further understand the mechanism of spontaneous emulsification. Co-surfactant addition promoted the emulsification via reducing the water/oil interfacial tension and viscosity. Ternary phase diagrams were constructed to investigate the phase behavior and designate the optimum systems. The alternative formulations were characterized for cloud point, dilution robustness, droplet size, polydispersity index (PDI) and transmission electron microscopy (TEM). In vitro dissolution study showed that the dissolution rate of optimized formulation (NCTD 10 mg/g, EO 50 wt.%, Cremophor EL 35 wt.%, ethylene glycol 15 wt.%) was slower than drug suspension under the same conditions, confirming that the developed SNEDDS formulation would exhibit sustained release potential.

Keywords:

• Nanoemulsion
• spontaneous emulsification
• interfacial tension
• oral bioavailability
• sustained release

Acknowledgements

The authors are grateful to School of Life Sciences (Northwestern Polytechnical University, China) for supporting a Malvern Zetasizer photo correlation spectroscopy (Nano ZS, Malvern Instrument, UK). The authors also sincerely appreciate John Richard Schrock (Emporia State University, USA) for revising the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

This research is supported by the Special Fund for the Public Interest (Agriculture) (200903052) by The Ministry of Science and Technology and The Ministry of Agriculture of China and the “13115” Sci-Tech Innovation Project of Shaanxi Province (2007 ZDKG-14).