释放介质组成对艾司奥美拉唑镁肠溶微丸释药行为影响的考察  

Investigation on Effect of Media Composition on Drug Release of Enteric-coated Esomeprazole Magnesium Pellets

作　　者：常功红 奚泉[1] 姚成丽[1] 陆伟根[1] 张栋梁 CHANG Gonghong;XI Quan;YAO Chengli;LU Weigen;ZHANG Dongliang(Shanghai Institute of Pharmaceutical Industry,China State Institute of Pharmaceutical Industry,Shanghai 201203)

机构地区：[1]中国医药工业研究总院上海医药工业研究院,上海201203

出　　处：《中国医药工业杂志》2020年第5期599-604,645,共7页Chinese Journal of Pharmaceuticals

摘　　要：本研究选择两阶段的释药方法,其中酸阶段pH 1.0、缓冲阶段pH 6.8,分别模拟胃和小肠的酸碱环境,考察了释放介质的离子强度和离子种类对自制艾司奥美拉唑镁肠溶微丸释药行为的影响。结果表明,释放介质的离子强度和阴离子种类对肠溶微丸的释药行为具有显著影响。在0.091~0.262 mol/L的离子强度范围内,肠溶性聚合物Eudragit L30D-55和主药艾司奥美拉唑镁的溶解性质均对释放介质的离子强度较敏感,是造成肠溶微丸的释药行为受释放介质离子强度显著影响的原因。而阴离子种类(盐酸盐和磷酸盐)对Eudragit L30D-55的溶解行为有显著影响,对主药几乎无影响,因此肠溶微丸的释药行为受到显著影响而未包肠溶衣的载药微丸的释药行为几乎不受影响。试验中未见阳离子(钾离子和钠离子)对肠溶微丸的释药行为产生显著性影响。因此,在肠溶制剂体外评价时应将离子强度、离子种类等因素的影响考虑在内。In this study, a two-stage pH-shift control strategy(acidic medium stage of pH 1.0 and buffer medium stage of pH 6.8 for simulating the pH environments of stomach and small intestine) was adopted for investigating the influences of ionic strength and ion species on drug release of the self-made enteric-coated pellets loaded with esomeprazole magnesium. The results showed that the drug release behaviors of the enteric-coated pellets were significantly affected by the ionic strength and anionic species of release medium. Within the tested scope of ionic strength(0.091-0.262 mol/L), the solubility properties of both enteric polymer Eudragit L30 D-55 and main drug esomeprazole magnesium were sensitive to the changes of ionic strength. It was the reason that the release behavior of the enteric-coated pellets was significantly affected by the ionic strength of release medium. Besides, anionic species(hydrochloride and phosphate) in medium had a significant effect on the release behaviors of the enteric-coated pellets which could also be attributed to solubility of Eudragit L30 D-55, while the drug release from the uncoated pellets was hardly affected by anions. No significant influences of cations(potassium and sodium ions) on drug release of the entericcoated pellets were observed. Therefore, the influences of ionic strength and ionic species should be considered in the in vitro evaluation of enteric preparations.

关 键 词：艾司奥美拉唑镁 肠溶微丸 体外释放 离子强度 离子种类 

分 类 号：R944.9[医药卫生—药剂学]