National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Wuhan Hubei, China,
MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan 430070, Wuhan Hubei, China.
Int J Nanomedicine. 2019 Mar 1;14:1619-1631. doi: 10.2147/IJN.S183479. eCollection 2019.
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.
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.
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.
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.
恩诺沙星（ENR）的适口性差、口服生物利用度变化大、对胃黏膜有刺激性、光不稳定性限制了其应用。本研究探索将固体脂质纳米粒（SLNs）与肠溶包衣结合制成肠溶颗粒，以克服这些缺点。
采用热匀化和超声乳化法制备载恩诺沙星 SLNs，然后通过湿法制粒和随后用聚丙烯酸树脂 II（PRII）包衣制备以 SLNs 为内核的肠溶颗粒。通过正交或单因素试验筛选优化处方。
以载药量（LC）和价格为考察指标的最佳 SLNs 由 10 mL 3%聚乙烯醇和 0.8 g 恩诺沙星与 2.4 g 硬脂酸组成。SLNs 的粒径、LC、多分散指数和 Zeta 电位分别为 308.5±6.3nm、15.73%±0.31%、0.352±0.015 和-22.3mv。最佳肠溶颗粒采用 15%PRII 作为包衣材料。肠溶颗粒在模拟肠液（SIF，pH=8）中的释放明显快于模拟胃液（SGF，pH=2），同时慢于 SLNs 和游离 ENR。颗粒在影响因素试验中表现出良好的稳定性。颗粒在每日采食量方面与对照组相似，高于恩诺沙星粉末和单包衣颗粒。与恩诺沙星可溶性粉相比，灌胃后肠溶颗粒的血浆浓度-时间曲线下面积和平均滞留时间分别从 4.26±0.85µgh/mL 和 6.80±2.28 小时增加到 11.24±3.33µgh/mL 和 17.97±4.01 小时。
肠溶颗粒结合 SLNs 与肠溶包衣显著提高了恩诺沙星的稳定性、适口性、缓释性能和口服生物利用度。这项新技术将是克服其他药物类似缺点的潜在措施。
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