Engineering of Long-Term Stable Transparent Nanoemulsion Using High-Gravity Rotating Packed Bed for Oral Drug Delivery

摘要

Background: Oil-in-water drug nanoemulsion forms drug delivery systems with high oral bioavailability. The conventional fabrication methods of nanoemulsion are low energy emulsification methods and high energy emulsification methods. However, both two methods are not ideal for industrial production. The problem of low energy emulsification methods is the high dosage of surfactant and co-surfactant which has potential biosecurity issues. What?is more, high energy emulsification methods have some disadvantages, like the destruction of drug components, the price of equipment and the difficulties of industrial production. Hence, there have been a few commercial drug nanoemulsions so far. Methods: In this work, we reported a novel method for the fabrication of stable and transparent drug nanoemulsion which contains hydrophilic drug rosuvastatin?(ROS) calcium or hydrophobic drug silybinin?(SYN) by using high-gravity rotating packed bed (RPB). The drug nanoemulsion was systematically characterized by droplet size, size distribution, stability and in vitro drug release as well as Caco-2 cells permeability. Results: Compared with the self-emulsification method (SE), high-gravity technology could reduce 75% amount of mixed surfactants. The as-prepared nanoemulsion exhibited a very narrow droplet size distribution with a size of 13.53?± 0.53 nm and a polydispersity index of 0.073?± 0.018. Meanwhile, the drug nanoemulsion was physicochemically stable at 25°C and 4°C for one-year storage. Furthermore, both ROS and SYN nanoemulsion displayed higher cell permeability and in vitro dissolution than that of commercial formulations. Conclusion: These results demonstrate that RPB can be a potential device to facilitate the industrial production of drug nanoemulsion.