摘要
目的制备含吲哚美辛的果胶氯化钙骨架片,考察影响其体外释放的因素。方法湿法制粒压片法制备吲哚美辛果胶氯化钙骨架片。分别考察氯化钙质量、果胶-氯化钙质量比以及释放介质对释放度的影响。通过溶蚀及吸水性试验,考察氯化钙的作用机制。结果骨架中果胶-氯化钙的质量比、药物-骨架质量比以及骨架的组成均可显著影响药物的释放。果胶氯化钙骨架片在不同的释放介质中表现出不同的释放行为。药物的释放与骨架的溶蚀及吸水速率呈正相关。在果胶酶(PectinexUltra SP-L)存在的条件下,骨架中药物的释放加快且释放完全。结论果胶氯化钙骨架片可通过果胶与钙离子的交联钙化形成强度较高的凝胶,降低了果胶的溶解度,具有缓控释效果,可通过进一步的设计达到结肠靶向的目的。
Abstract
OBJECTIVE To prepare pectin-calcium chloride matrix tablets and evaluate indomethacin release profiles in vitro.METHODS Wet granulation technique was employed to prepare pectin-calcium chloride matrix tablets. The amount of calcium chloride, the mass ratio of calcium chloride-pectin and release media on drug release profiles were investigated. Matrix erosion and water uptake were performed to elucidate the mechanisms of calcium chloride on drug release. RESULTS The ratio of pectin-calcium chloride and mass ratio of drug-matrix were important factors on the drug release. The pectin-calcium chloride matrix tablets had different release profile in various media. The drug release rate was positively correlated to matrix erosion rate and the relative water uptake rate. The drug released quickly and completely with the Pectinex Ultra SP-L.CONCLUSION The pectin-calcium chloride-based matrix tablets can form relative rigid gel by cross-linking between pectin and calcium ions in situ. This kind of system has potential to be used to target drugs to the colon.
关键词
果胶 /
氯化钙 /
释放度 /
溶蚀 /
吸水 /
结肠靶向
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Key words
pectin /
calcium chloride /
release /
erosion /
water uptake /
colon targeting
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魏秀莉;孙宁云;吴宝剑;吴伟;徐惠南.
氯化钙对吲哚美辛果胶骨架片体外释放的影响[J]. 中国药学杂志, 2006, 41(23): 1804-1808
WEI Xiu-li;SUN Ning-yun;WU o-jin;WU Wei;XU Hui-nn.
Effect of Calcium Choloride on Indomethacin Release from Pectin-Based Matrix Tablets [J]. Chinese Pharmaceutical Journal, 2006, 41(23): 1804-1808
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参考文献
[1] MOOTER G V，KINGET R. Oral colon-specific drug delivery： a review[J] .Drug Delivery，1995，2：81-96.
[2] KOPECEK J，KOPECKOVA P，BRONDSTED H，et al. Polymers for colon-specific drug delivery[J] .J Controlled Release，1992，19：121-130.
[3] SINHA V R，KUMRIA R. Polysaccharides in colon-specific drug delivery[J] .Int J Pharm，2001，224：19-38.
[4] ASHFORD M，FELL J T，ATTWOOD D，et al. An evaluation of pectin as a carrier for drug targeting to the colon[J] .J Controlled Release，1993，26： 213-220.
[5] ASHFORD M，FELL J T，ATTWOOD D，et al. Studies on pectin formulations for colonic drug delivery[J] .J Controlled Release，1994，30： 225-232.
[6] WAKERLY Z，FELL J T，ATTWOOD D，et al. Pectin/ethyl cellulose film coating formulations for colonic drug delivery[J] .Pharm Res，1996，13： 1210-1212.
[7] ADKIN A D，KENYON C J，LERNER E I，et al. The use of scintigraphy to provide proof of concept for novel polysaccharide preparation designed for colonic drug delivery[J] . Pharm Res，1997，14：103-107.
[8] RUBINSTEIN A，RADAI R. In vitro and in vivo analysis of colon specificity of calcium pectinate formulation[J] .Eur J Pharm Biopharm，1995，41：291-295.
[9] KUBO W，MIYAZAKI S，DAIRAKU M，et al. Oral sustained delivery of ambroxol from in situ-gelling pectin formulation[J] .Int J Pharm，2004，271：233-240.
[10] MANUNZA B，DEIANA S，PINTORE M，et al. Interaction of Ca2+ and Na+ ions with polygalactruonate chains： a molecular dynamics study[J] .Glyconjug J，1998，15：297-300.
[11] YOO S H，FISHMAN M L，SAVARY B J，et al. Monovalent salt-induced gelation of enzymatically de-esterified pectin[J] .J Agric Food Chem，2003，51： 7410-7417.
[12] LIU L，FISHMAN M L，KOST J，et al. Pectin-based systems for colon-specific drug delivery via oral route[J] .Biomaterials，2003，24：3333-3343.
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脚注
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基金
上海市科技发展基金资助项目(024319114);上海市教委优秀青年教师后备人选资助项目(03YQHB008)
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