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.
Developing a targeted oral delivery system to improve the efficacy of veterinary antibiotics and reduce their consumption and environmental risks is urgent. To achieve the duodenum-targeted release of tilmicosin, the enteric granule containing tilmicosin-loaded solid lipid nanoparticles (TIL-SLNs) was prepared based on its absorption site and transport characteristics. The in vitro release, release mechanisms, stability, palatability, and pharmacokinetics of the optimum enteric granules were studied. The intestine perfusion indicated that the main absorption site of tilmicosin was shifted to duodenum from ileum by TIL-SLNs, while, the absorption of TIL-SLNs in the duodenum was hindered by P-glycoprotein (P-gp). In contrast with TIL-SLNs, the TIL-SLNs could be more effectively delivered to the duodenum in intact form after enteric coating. Its effective permeability coefficient was enhanced when P-gp inhibitors were added. Compared to commercial premix, although the TIL-SLNs did not improve the oral absorption of tilmicosin, the time to reach peak concentration (Tmax) was obviously shortened. After the enteric coating of the granules containing SLNs and P-gp inhibitor of polysorbate-80, the oral absorption of tilmicosin was improved 2.72 fold, and the Tmax was shortened by 2 h. The combination of duodenum-targeted release and P-gp inhibitors was an effective method to improve the oral absorption of tilmicosin.
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