恩诺沙星缓释颗粒剂的研究

发布时间：2018-03-25 08:41

  本文选题：恩诺沙星　切入点：缓释颗粒　出处：《武汉工程大学》2015年硕士论文

【摘要】：恩诺沙星是广谱抗菌素,属于喹诺酮类第三代药物,由于其高效、低毒的抗菌特点,在1996年被FDA批准为动物专用药,也是第一个获国际认可的动物专用抗菌药。普通的恩诺沙星制剂因味苦口感不佳或频繁给药等导致动物的应激反应,出现拒食现象,而使它们因各种细菌感染的疾病得不到很好地预防和治疗,降低了成活率。为了掩盖恩诺沙星的苦味和提高治疗效果,本文结合缓释材料的特性,制备了12小时内缓慢释放的恩诺沙星缓释颗粒剂,以期达到减少给药次数,同时由于降低了药物溶出速度而起到改善药物口感的作用。具体进行了以下几方面的工作:建立了恩诺沙星缓释颗粒剂的含量测定方法和体外累积释放度的测定方法。通过处方前研究,采用单因素实验和正交实验,以相似因子f2值为评价指标,筛选出了最佳制备处方为:恩诺沙星20%、羟丙基甲基纤维素k100(HPMCk100)25%、硬脂酸8%、乳糖35%、粘合剂为5%聚乙烯吡咯烷酮k-30(PVPk-30)醇溶液;制备工艺为:以亲水凝胶骨架材料羟丙基甲基纤维素(HPMCk100)与蜡质材料硬脂酸的混合物为骨架材料,采用溶剂熔融法,先制备恩诺沙星的固体分散体,再与乳糖、聚乙烯吡咯烷酮K-30(PVPk-30)等辅料混合制备颗粒,即得具有缓释效果的恩诺沙星颗粒剂。并以最优处方制备三批放大样,对最优处方和工艺进行验证。根据相关标准对恩诺沙星缓释颗粒剂的质量进行研究,系统地考察了各项质量指标,如粒度、性状、鉴别、有关物质、药物含量测定和累计释放度测定等,结果表明该制剂的制备工艺可行,产品质量稳定,可以为后期拟定质量标准提供科学、合理、有效的依据。最后考察了恩诺沙星缓释颗粒剂的稳定性。影响因素实验结果表明,制备的恩诺沙星缓释颗粒在相对湿度75%的条件下放置10天,颗粒略有吸湿,而在60℃高温和4500Lx±500Lx强光照条件下,样品质量稳定,各项指标均无明显变化。模拟市售包装的恩诺沙星缓释颗粒在40±2℃温度,65%±5%的相对湿度的实验环境下放置6个月,进行加速试验;在25±2℃温度,60%±5%的相对湿度环境下放置6个月,进行长期实验,结果显示样品的各项质量均未发生明显变化,表明该产品质量比较稳定。
[Abstract]:Enrofloxacin is a broad-spectrum antibiotic, belonging to the third generation of quinolones. Because of its high efficiency and low toxicity, enrofloxacin was approved by FDA as animal medicine in 1996. It is also the first internationally recognized animal-specific antimicrobial agent. Common enrofloxacin formulations, which suffer from poor taste and bitter taste or frequent administration of drugs, cause stress reactions in animals and lead to anti-feeding phenomena. In order to cover up the bitter taste of enrofloxacin and improve the therapeutic effect, this paper combines the properties of slow release material, in order to cover up the bitterness of enrofloxacin and improve the therapeutic effect. Slow release of enrofloxacin granules was prepared within 12 hours in order to reduce the frequency of administration. At the same time, it can improve the taste of the drug by reducing the dissolution rate of the drug. The following work has been done: the method of determination of the content of enrofloxacin sustained-release granules and the determination of cumulative release in vitro have been established. Methods. Through the pre-prescription study, By using single factor experiment and orthogonal experiment, the best preparation prescription of enrofloxacin 20, hydroxypropyl methyl cellulose k100 HPMCk100, stearic acid 8, lactose 35 and binder 5% polyvinylpyrrolidone k-30PVPk-30 alcohol solution was selected. The preparation process was as follows: the mixture of hydrophilic gel framework HPMCk100) and waxy stearic acid was used to prepare enrofloxacin solid dispersion, then lactose, by solvent melting method. Poly (vinylpyrrolidone) K-30 (PVPk-30) and other excipients were mixed to prepare particles, namely enrofloxacin granules with slow-release effect, and three batches of magnified samples were prepared with the best formulation. The quality of enrofloxacin sustained-release granules was studied according to the relevant standards. The quality indexes, such as particle size, properties, identification, related substances, were systematically investigated. The results showed that the preparation process of the preparation was feasible and the product quality was stable, which could provide a scientific and reasonable method for the later formulation of the quality standard. Finally, the stability of enrofloxacin sustained release granules was investigated. The experimental results showed that the prepared enrofloxacin sustained release granules were slightly hygroscopically absorbed at 75% relative humidity for 10 days. However, under the conditions of high temperature of 60 鈩，

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