Enteric polymers as binders and coating materials in multiple-unit site-specific drug delivery systems
Enteric polymers as binders and coating materials in multiple-unit site-specific drug delivery systems
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DOI：
10.1016/s0928-0987(98)00032-3
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发表时间：
1999-02-01
影响因子：
4.6
通讯作者：
Autere, AM
中科院分区：
文献类型：
--
作者：
Marvola, M;Nykänen, P;Autere, AM
本研究的目的是开发一种多单元、位点特异性的药物制剂，允许靶向药物在结肠中释放。首先，测试了含有各种肠道聚合物作为粘合剂的基质微球的特性。然后在配方中加入肠溶包衣。以布洛芬和呋塞米为模型药物。前者通过胃肠道吸收，后者仅从上半身吸收。采用甲基丙烯酸酯共聚物、羟丙基甲基乙酸琥珀酸酯纤维素和邻苯二甲酸酯醋酸纤维素作为肠道聚合物。产品的特性首先通过不同ph值的溶解研究进行测试，然后通过健康志愿者的生物利用度研究。主要结论是，通过制备薄膜包膜基质微球，药物可以在小肠和结肠的远端释放，其中溶解在pH值接近7的肠道聚合物既可以作为微球的粘合剂，也可以作为包衣材料。这一结论是基于下述发现：所研制的制剂对布洛芬的吸收是充分的，滞后时间约为2小时，t（最大）值为4-5小时，而类似产品对速尿的吸收可以忽略不计。研究还发现，这种未包衣的微丸可能代表速尿的缓释制剂，速尿是一种有问题的药物，就缓释产品而言。(C) 1999 Elsevier Science S.A.版权所有
The aim of this study was to develop a multiple-unit, site-specific drug formulation allowing targeting of drug release in the colon. Initially, characteristics of matrix pellets containing various enteric polymers as binders were tested. An enteric coating was then added to the formulations. Ibuprofen and furosemide were used as model drugs. The former is absorbed throughout the gastrointestinal tract, the latter only from upper parts. Methacrylate copolymers, hydroxypropyl methylcellulose acetate succinates and cellulose acetate phthalate were used as enteric polymers. The properties of the products were initially tested via dissolution studies at different pHs, then via bioavailability studies in healthy volunteers. The main conclusion was that drug release can be targeted on the distal past of the small intestine and the colon by preparing film-coated matrix pellets in which enteric polymers dissolving at pH approximate to 7 have been used both as binders in the pellets and as coating material. This conclusion is based on the finding that absorption of ibuprofen from the formulations developed was adequate, with a lag-time of about 2 h and t(max) values at 4-5 h, where as absorption of furosemide from the analogous products was negligible. It was also found that uncoated pellets as such could represent a slow-release formulation for furosemide, a problem drug as far as modified-release products are concerned. (C) 1999 Published by Elsevier Science S.A. All rights reserved.