Solid lipid nanoparticles with enteric coating for improving stability, palatability, and oral bioavailability of enrofloxacin

Abstract

Background

The poor palatability, variable oral bioavailability, stimulation to gastric mucosa, and light instability limited the application of enrofloxacin (ENR). The enteric granules combining solid lipid nanoparticles (SLNs) with enteric coating were explored to overcome these disadvantages.

Materials and methods

ENR-loaded SLNs were produced by a hot homogenization and ultrasonic emulsification method and the enteric granules with SLNs as inner core were prepared by wet granulation followed by coating using polyacrylic resin II (PRII). The formulation was optimized by using orthogonal or single factor test screening.

Results

The optimal SLNs with loading capacity (LC) and price as inspection indexes were consisted of 10 mL 3% polyvinyl alcohol per 0.8 g ENR and 2.4 g octadecanoic acid. The sizes, LC, polydispersion index, and zeta potential of the SLNs were 308.5±6.3 nm, 15.73%±0.31%, 0.352±0.015, and −22.3 mv, respectively. The best enteric granules were used 15% PRII as coating materials. The release of the enteric granules in simulated intestine fluid (SIF, pH=8) was significantly faster than in simulated gastric fluid (SGF, pH=2) and simultaneously slower than those of SLNs and native ENR. The granules showed good stability in influencing factor experiment. The granules displayed a similar daily feed intake as the control group and higher daily feed intake than ENR powder and single-coating granules. Compared to the ENR soluble powder, the area under the plasma concentration–time curve and mean retention time of the enteric granules after intragastric administration were increased from 4.26±0.85 µg h/mL and 6.80±2.28 hours to 11.24±3.33 µg h/mL and 17.97±4.01 hours, respectively.

Conclusion

The enteric granules combination SLNs with enteric coating significantly improved the stability, palatability, sustained-release performance and oral bioavailability of ENR. The novel technology will be a potential measure to overcome the similar disadvantages of other drugs.

Keywords:

• enrofloxacin
• solid lipid nanoparticles
• enteric coating
• palatability
• bioavailability
• light stability

Acknowledgments

This work was supported by the National Key Research and Development Program of China (2017YFD0501402) and the National Natural Science Foundation of China (grant no 31772797).

Disclosure

The authors report no conflicts of interest in this work.