5-氨基水杨酸结肠定位缓释胶囊的制备及释放度研究
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摘要
目的:制备5-氨基水杨酸结肠定位缓释微丸胶囊,建立其体外药物释放度分析方法,并研究其体外释放行为。方法:以挤出滚圆法制备微丸丸芯,采用Mini-glatt流化床进行包衣,研究了不同型号MCC、HPMC、硬脂酸镁、枸橼酸、Eudragit NE30D及其用量、包衣增重等对体外释放的影响,采用转篮法[100r·min~(-1),(37±0. 5)℃]测定5-氨基水杨酸结肠定位缓释微丸的体外释放度;以f_2相似因子法评价3批自制制剂与对照制剂Apriso~(TM)的释放相似性。结果:成功筛选出了合理、科学的处方,制备了均一、可控的5-氨基水杨酸结肠定位缓释微丸胶囊。在pH 6. 0 PBS,pH 6. 8 PBS与pH 7. 4 PBS中,自制3批制剂与对照制剂的释放度f_2值均大于50,且释放度无显著性差异(P> 0. 05),重复性良好。结论:该制备方法可行,建立的释放度测定方法操作简便、准确;自制制剂有结肠定位缓释功能,减少了给药次数,增强了患者的顺应性。
Objective: To prepare 5-amino salicylic acid colon specific sustained-release pellet capsules,establish drug release analysis method and study its release behavior in vitro. Methods: The cores of pellet were prepared by extrusion circle method and coated with mini-glatt fluidized bed. The effects of different types of MCC,HPMC and their dosages,dosages of magnesium stearate,citric acid,eudragit NE30D and gaining of coating weight were studied. The release of 5-amino salicylic acid colon specific sustained-release capsules was measured by basket method (100 RMP,37 ± 0. 5 ℃),and the similarity between three batches of self-made preparations and reference pellet capsules AprisoTMwas evaluated by f_2 similarity factor method. Results: A reasonable and scientific prescription was successfully screened. Uniform and controllable 5-amino salicylic acid colon specific sustained release pellet capsules were prepared. In pH 6 PBS,pH 6. 8 PBS and pH 7. 4 PBS,the f_2 values of the release of three batches of self-made preparations with the original preparation were all greater than 50,the release rates were not significantly different (P > 0. 05),and the reproducibility was good. Conclusion: The established preparation method for 5-amino salicylic acid colon specific sustained release pellet capsules is feasible,simple and accurate.The self-made preparation has the properties of colon-localization and sustained-release,which can reduce the frequency of dosing and enhance patients' compliance.
Objective: To prepare 5-amino salicylic acid colon specific sustained-release pellet capsules,establish drug release analysis method and study its release behavior in vitro. Methods: The cores of pellet were prepared by extrusion circle method and coated with mini-glatt fluidized bed. The effects of different types of MCC,HPMC and their dosages,dosages of magnesium stearate,citric acid,eudragit NE30D and gaining of coating weight were studied. The release of 5-amino salicylic acid colon specific sustained-release capsules was measured by basket method (100 RMP,37 ± 0. 5 ℃),and the similarity between three batches of self-made preparations and reference pellet capsules AprisoTMwas evaluated by f_2 similarity factor method. Results: A reasonable and scientific prescription was successfully screened. Uniform and controllable 5-amino salicylic acid colon specific sustained release pellet capsules were prepared. In pH 6 PBS,pH 6. 8 PBS and pH 7. 4 PBS,the f_2 values of the release of three batches of self-made preparations with the original preparation were all greater than 50,the release rates were not significantly different (P > 0. 05),and the reproducibility was good. Conclusion: The established preparation method for 5-amino salicylic acid colon specific sustained release pellet capsules is feasible,simple and accurate.The self-made preparation has the properties of colon-localization and sustained-release,which can reduce the frequency of dosing and enhance patients' compliance.
引文
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[13]周静.固体药物制剂的体外溶出度的统计学评价分析[J].中西医结合心血管病电子杂志,2017,5(13):180-181.
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[15]RAJESH G,CHAMAN K,RAMESH P.Extrusion and spheronization in the development of oral controlled-release dosage forms[J].Pharm Sci Technol Tod,1999,2(4):160-170.
[16]PRETORO D,ZEMA L,GAZZANIGA A,et al.Extrusion-spheronisation of highly loaded 5-ASA multiparticulate dosage forms[J].Int J Pharm,2010,402(1-2):153-164.
[17]王玉鹏,赵丽华,胡容峰.缓释骨架材料在药物制剂中的应用[J].中国药房,2007,18(25):1987-1988.
[18]黄献,刘裕恒,莫志江.用SPSS拟合药物溶出度Weibull参数[J].中国药房,2006,17(14):1079-1081.
[19]周思宇,谢作都,叶添宝,等.5-氨基水杨酸的结肠靶向释药系统[J].中国现代应用药学,2017,34(8):1205-1210.
[20]刘慧敏,黄麟杰,郑芳,等.多糖作为载体在5-氨基水杨酸口服结肠定位系统中的研究进展[J].实用药物与临床,2017,20(12):1445-1449.
[2]陈治水,王新月.溃疡性结肠炎中西医结合诊疗共识[J].中国中西医结合消化杂志,2010,18(6):416-419.
[3]孙平良,钟元帅,李裕波,等.溃疡性结肠炎中医病因病机研究进展[J].中医研究,2016,29(4):71-74.
[4]李梅,张苏闽.溃疡性结肠炎病因分析及预防[J].中医学报,2012,27(10):1343-1345.
[5]ROHINI V,MILLIE L.Contemporary management of ulcerative colitis[J].Curr Gastroenterol Rep,2018,20:12.
[6]杨泽云.溃疡性结肠炎的发病机制与治疗进展[J].临床合理用药杂志,2015,8(30):180-181.
[7]赵亚绘,张赫然,王彦竹,等.美沙拉嗪结肠靶向制剂研究进展[J].中国新药杂志,2015,24(12):1387-1392.
[8]MAYUR P,AVANI A.Development of a novel tablet-in-capsule formulation of mesalamine for inflammatory bowel disease[J].Pharm Dev Technol,2013,18(2):390-400.
[9]KARAGOZIAN R,BURAKOFF R.The role of mesalamine in the treatment of ulcerative colitis[J].Ther Clin Risk Manag,2007,3(5):893-903.
[10]HIRAYAMA M,TODA R,OZAKI T.Concentration dependence of 5-aminosalicylic acid pharmacological actions in intestinal mucosa after oral administration of a p H-dependent formulation[J].Mol Pharm,2011,8(4):1083-1089.
[11]曲东,林森.氨基水杨酸类药物治疗炎症性肠病的应用进展[J].世界临床药物,2008,29(12):727-730.
[12]崔艳丽,史亦丽,张岩.溃疡性结肠炎治疗药物美沙拉秦剂型的发展与应用[J].中国现代医学杂志,2009,19(24):3763-3766.
[13]周静.固体药物制剂的体外溶出度的统计学评价分析[J].中西医结合心血管病电子杂志,2017,5(13):180-181.
[14]王乐.5-氨基水杨酸结肠定位释药片的研制[D].上海:上海医药工业研究院,2006.
[15]RAJESH G,CHAMAN K,RAMESH P.Extrusion and spheronization in the development of oral controlled-release dosage forms[J].Pharm Sci Technol Tod,1999,2(4):160-170.
[16]PRETORO D,ZEMA L,GAZZANIGA A,et al.Extrusion-spheronisation of highly loaded 5-ASA multiparticulate dosage forms[J].Int J Pharm,2010,402(1-2):153-164.
[17]王玉鹏,赵丽华,胡容峰.缓释骨架材料在药物制剂中的应用[J].中国药房,2007,18(25):1987-1988.
[18]黄献,刘裕恒,莫志江.用SPSS拟合药物溶出度Weibull参数[J].中国药房,2006,17(14):1079-1081.
[19]周思宇,谢作都,叶添宝,等.5-氨基水杨酸的结肠靶向释药系统[J].中国现代应用药学,2017,34(8):1205-1210.
[20]刘慧敏,黄麟杰,郑芳,等.多糖作为载体在5-氨基水杨酸口服结肠定位系统中的研究进展[J].实用药物与临床,2017,20(12):1445-1449.