醋氯芬酸肠溶微丸的制备

发布时间：2018-11-26 17:04

【摘要】：醋氯芬酸是一种新型较强效的非甾体抗炎药，，主要用于治疗风湿性关节炎（RA）、骨关节炎等炎症引起的疼痛。非甾体抗炎药对胃有刺激性作用，可能导致胃部出血，将这类药物制成肠溶制剂可减少刺激作用。本课题的目的在于制备醋氯芬酸肠溶微丸，减少这类药物的刺激性。实验建立了HPLC法测定醋氯芬酸含量，紫外分光光度法测定醋氯芬酸肠溶微丸的释放度并进行了方法学研究。实验采用离心造粒工艺制备醋氯芬酸载药微丸，滑石粉作为隔离层材料，以尤特奇L30D-55（Eudragit L30D-55）作为肠溶包衣材料，用流化床进行包衣，通过单因素考察法优化处方与工艺参数，筛选出最佳的处方及工艺参数，并进行了中试放大。建立了醋氯芬酸生物样品的测定方法，考察了参比制剂与试验制剂在家兔体内的药代动力学过程。本实验制备的醋氯芬酸肠溶微丸的粒径为18~24目（0.8~1.0mm），测得休止角为28.5°，小于30°，平均载药量31.25%，在酸pH1.0中2h的释放量小于标示量的5.00%，在pH6.8磷酸缓冲盐溶液中45min累积释放量超过标示量的70.00%。中试生产制备醋氯芬酸载药微丸过程收率为88.62%，流化床包衣过程收率73.65%。测得醋氯芬酸肠溶微丸和醋氯芬酸肠溶胶囊的血药浓度达峰时间分别为6.00±0.50h和4.00±0.90h；最高血药浓度分别为8.40±0.70μg·mL-1和9.08±0.60μg·mL-1；药时曲线下面积(AUC0-t)分别为105.11±7.09(μg·mL-1)·h和88.54±15.22(μg·mL-1)·h。实验结果表明，醋氯芬酸肠溶微丸的耐酸力、重现性优于上市两肠溶制剂，具有进一步开发的价值。
[Abstract]:Acaclofenac is a new and effective nonsteroidal anti-inflammatory drug which is mainly used to treat pain caused by inflammation such as rheumatoid arthritis (RA),) osteoarthritis. Non-steroidal anti-inflammatory drugs (NSAIDs) have irritant effects on the stomach, which may lead to gastric bleeding. The aim of this study is to prepare enteric micropellets of acaclofenac to reduce the irritation of these drugs. HPLC method was established to determine the content of acaclofenac and UV spectrophotometry was used to determine the release of acaclofenac enteric pellets. In this experiment, acaclofenac loaded pellets were prepared by centrifugal granulation process, talc powder was used as the separation layer material, Uttage L30D-55 (Eudragit L30D-55) was used as enteric coated material, and the coating was carried out in fluidized bed. The optimum prescription and technological parameters were optimized by single factor investigation method, and the pilot-scale amplification was carried out. A method for the determination of acaclofenac in biological samples was established. The pharmacokinetics of reference preparation and test preparation in rabbits was investigated. The particle size of enteric-coated pellets of acaclofenac was 184mesh (0.8~1.0mm), the angle of repose was 28.5 掳, less than 30 掳, the average drug load was 31.255.The release amount in acid pH1.0 for 2 hours was less than 5.00% of the labeled amount. The cumulative release of 45min in the buffer solution of pH6.8 phosphoric acid exceeded 70.00g of the labeled amount. The yield of micropellets was 88.62, and that of fluidized bed coating was 73.65. The peak time of blood drug concentration was 6.00 卤0.50h and 4.00 卤0.90h, respectively, and the highest concentration was 8.40 卤0.70 渭 g mL-1 and 9.08 卤0.60 渭 g mL-1;, respectively. The area under the curve (AUC0-t) was 105.11 卤7.09 (渭 g mL-1) h and 88.54 卤15.22 (渭 g mL-1) h, respectively. The results showed that the acid-resistance and reproducibility of acidophilic acid enteric-coated pellets were superior to those of the two enteric dissolution preparations, and had the value of further development.
【学位授予单位】：河北科技大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943

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