【作者】 代奕；

【导师】 李三鸣； 庄殿友；

【作者基本信息】 沈阳药科大学 ， 药剂学， 2006， 硕士

【摘要】 盐酸阿比朵尔是用于治疗和预防由A、B型流感病毒引起的流感及急性呼吸道病毒感染的新型抗病毒药物，同时具有免疫调节、干扰诱导和抗氧化的性质。由于目前国内主要是盐酸阿比朵尔速释制剂，每天服用4次，血药浓度波动较大。为此本文以减少给药次数，降低血药浓度波动，提高患者用药顺从性为目的，制备了盐酸阿比朵尔缓释微丸。 建立了紫外分光光度法对盐酸阿比朵尔缓释微丸进行含量、释放度及基本性质的测定，分别经方法学考察适用于本品的体外质量控制。处方前研究表明：盐酸阿比朵尔在水、0.1mol·L^-1盐酸和pH6.8磷酸盐中的溶解度较低，在0.5％SDS中的溶解度较高。阿比朵尔的表观油水分配系数呈现pH依赖性，在pH6.8时达最大值。 采用大鼠在体灌流实验方法研究了盐酸阿比朵尔在大鼠肠道的吸收情况。大鼠在体肠吸收动力学试验结果表明：盐酸阿比朵尔在整个肠道均有较好的吸收，十二指肠、空肠、回肠和结肠部位的表观吸收系数依次为13.6、11.9、9.8和6.1μL·min^-1·cm^-1，各个肠段间的吸收分数和表观吸收系数有明显差异；肠灌流液中药物浓度和Tween-80的浓度对盐酸阿比朵尔的大鼠小肠表观吸收系数无明显影响；肠灌流液pH值对盐酸阿比朵尔的鼠肠表观吸收系数有显著性影响，偏酸性吸收优于近中性；药物在大鼠体内的吸收机制为被动扩散。 采用挤出滚圆法制备盐酸阿比朵尔微丸。通过单因素考察和正交试验筛选处方和制备工艺，结果目标粒径18～24目的微丸收率约80％，微丸外观圆整，有较强的机械强度。 用流化床悬浮包衣法对盐酸阿比朵尔微丸进行缓释包衣。以释放度为指标，采用Eudragit RS30D／RL30D水分散体混合作为包衣材料，对增塑剂、抗粘剂、抗静电剂、包衣增重及老化时间等进行了考察，确定了最佳包衣工艺和包衣液处方组成。释药机制探讨表明：体外释药具有明显的缓释特征，释放机制符合一级释药模型。 建立了高效液相色谱法测定家犬血浆中盐酸阿比朵尔的浓度。以普通片为对照，测定了缓释微丸在3只家犬体内的药物动力学和相对生物利用度，采用统计矩法对血药浓度数据进行处理。结果表明：普通片与缓释微丸的峰浓度(C_max)分别为1036.5和551.9ng·mL^-1，达峰时间(T_max)分别为1.67和6h，体内平均滞留时间（MRT）分别为4.14和9.87h。缓释微丸相对于普通片的生物利用度为103.7％，且体外释药与体内吸收有较好的相关性，两更多还原

【Abstract】 Arbidol Hydrochloride was selected as a new antiviral drug for the treatment and prophylaxis of influenza and other acute respiratory viral infections （ARVI）. At the same time, Arbidol had the immunomodulating activity, capacity of inducing interferon and antioxidant property. Nowadays Arbidol is taken 4 times daily and shows bigger fluctuation in the drug concentration. The aim of this work was desigened to develop a kind of Arbidol sustained-release pellets, which would reduce the dosing frequency, narrow the blood concentration fluctuation and be more convenient for patients to use.UV method was developed for assaying the drug content and drug release of Arbidol sustained release pellets. The method was monitored by methodology and it was simple, accurate to be used in vitro. The preformulation results showed that the apparent solubility of Arbidol in water, 0.1NHC1 and pH 6.8PBS were low, and in 0.5%SDS was high. The apparent partition coefficient in oil and water of Arbidol was dependent on pH, and the maximum value appeared at pH6.8.To investigate the absorption characters of Arbidol in the intestine, the absorption kinetics and the absorption sites were studied by utilizing the rat intestinal absorption single pass perfusion model in situ. The results of perfused rat intestinal model showed that Arbidol could be well absorbed at all segments of intestine in rats. The apparent absorption rate constants at duodenum, jejunum, ileum and colon were 13.6、11.9、9.8 and 6.1 μL·min^-1·cm^-1, respectively. The concentration of drug and Tween-80 had no evident influence on the absorption rate constants. The pH of drug solutions had an effect on the absorption constants, and the absorption was better at low pH. It was showed that the absorption of Arbidol was the passive diffusion mechanism.Extrusion-spheronization technology was used to prepare Arbidol pellets. Technology factors of preparing pellets and formulation factors were investigated and optimized by the influence factors test and orthogonal design test. It was discovered that the yield of the objective更多还原