氟苯尼考缓释颗粒的制备及体外释放特性

【目的】延长药物有效血药浓度的维持时间,产生持续稳定的抑菌作用,避免多剂量连续使用氟苯尼考产生胚胎毒性和免疫抑制。【方法】以硬化油、聚乙二醇、甘油酯为辅料,采用离心喷雾干燥制粒技术法制备氟苯尼考缓释颗粒,高效液相色谱法(HPLC)测定氟苯尼考含量。以药物在不同释放介质(pH 1.2盐酸缓冲液、pH 4.3醋酸缓冲液和pH6.8磷酸缓冲液)中的释放特性为指标,对氟苯尼考粉和自制的氟苯尼考缓释颗粒进行溶出试验,考察体外释放特性。【结果】4个批次制备的氟苯尼考缓释颗粒中氟苯尼考实际含量在标示含量中的占比分别为99.19%、100.01%、97.45%和100.72%,相对标准偏差(RSD)分别为0.82%、0.86%、0.77%和0.24%。氟苯尼考粉在0.25 h内完全释放,自制的氟苯尼考缓释颗粒在模拟胃液环境(pH 1.2盐酸缓冲液)基本不释放,在模拟肠液环境(pH 4.3醋酸缓冲液和pH6.8磷酸缓冲液)缓慢释放,5 h内释放量达95%以上。【结论】自制的氟苯尼考缓释颗粒中药物分布较均匀,符合中国兽药典要求。相比于氟苯尼考粉,氟苯尼考缓释颗粒表现出良好的耐酸性体外缓释性,可为后续的临床试验研究和临床使用药物提供参考依据。

Preparation and in vitro release characteristics of florfenicol sustained-release granules

Objective To prolong the maintenance time of the effective blood concentration of the drug, generate a sustainable and stable bacteriostatic action, and avoid embryotoxicity and immunosuppression in multi-dose continuous use of florfenicol.Method The test used hardened oil, polyethylene glycol and glyceride as auxiliary materials. The florfenicol sustained-release granules were prepared by centrifugal spray drying granulation method, and the content of florfenicol was determined by high performance liquid chromatography (HPLC). Using release characteristics of the drug in different media (pH 1.2 hydrochloric acid buffer, pH 4.3 acetate buffer and pH 6.8 phosphate buffer) as indicators, the dissolution tests of florfenicol powder and self-made florfenicol sustained-release granules were carried out to investigate their in vitro release performances.Result The percentages of florfenicol actual contents in indicated contents of florfenicol sustained-release granules prepared in four batches were 99.19%, 100.01%, 97.45% and 100.72%, and the relative standard deviations (RSD) were 0.82%, 0.86%, 0.77% and 0.24% respectively. The florfenicol powder was completely released within 0.25 h. The self-made florfenicol sustained-release granules were substantially not released in simulated gastric fluid environment (pH 1.2 hydrochloric acid buffer), and released slowly under simulated intestinal fluid environment (pH 4.3 acetate buffer and pH 6.8 phosphate buffer) with the release amount of over 95% within 5 h.Conclusion The drug in self-made florfenicol sustained-release granules is homogeneous distributed, and the granules conform to China veterinary pharmacopoeia. Compared with florfenicol powder, florfenicol sustained-release granules show good acid resistance and in vitro sustained-release performance, which provides a reference for subsequent clinical trial research and clinical use of drugs.