Evaluation of the drug release patterns and long term stability of aqueous and organic coated pellets by using blends of enteric and gastrointestinal insoluble polymers.
Evaluation of the drug release patterns and long term stability of aqueous and organic coated pellets by using blends of enteric and gastrointestinal insoluble polymers.
复制标题
DOI：
10.1016/j.ijpharm.2009.07.013
复制
发表时间：
2009-10
影响因子：
5.8
通讯作者：
H. Kranz;S. Gutsche
中科院分区：
文献类型：
--
作者：
H. Kranz;S. Gutsche
本研究的主要目的是确定一种有效的工具，以调整药物从水性和有机乙基纤维素（胃肠道不溶性聚合物）包衣微丸的释放模式，并评估薄膜包衣的长期稳定性。在25°C/60%RH（环境条件）和40°C/75%RH（应力条件）下开放和封闭储存长达24个月期间监测药物释放。琥珀酸瓦他拉尼是一种表现出pH依赖性溶解度的难溶性药物，其从纯乙基纤维素包衣微丸中的释放缓慢，与包衣和释放介质的类型无关。通过将肠溶聚合物甲基丙烯酸/丙烯酸乙酯共聚物（以水性Kollicoat MAE 30 DP分散体或Kollicoat MAE 100 P的有机溶液形式施用）添加到乙基纤维素中，可以实现宽范围的药物释放模式。对于水性薄膜包衣，将Kollicoat MAE 30 DP添加到乙基纤维素分散体中，导致在环境和强制降解条件下密闭储存期间药物释放动力学不变。添加的肠溶聚合物的储存稳定作用可能是由于与乙基纤维素相比，Kollicoat MAE 30 DP在成膜过程中更亲水，并改善了聚合物颗粒聚结。然而，在强制降解条件下含水包衣乙基纤维素：Kollicoat MAE 30 DP微丸的开放储存期间，由于聚合物颗粒进一步逐渐聚结，药物释放降低。相比之下，在环境和强制降解条件下储存的有机包衣乙基纤维素：Kollicoat MAE 100 P微丸的药物释放速率没有变化，这可以通过成膜过程中的差异来解释。这清楚地表明，所提出的将甲基丙烯酸/丙烯酸乙酯共聚物添加到乙基纤维素薄膜包衣中与有机包衣工艺组合的概念能够实现宽范围的药物释放模式并克服储存不稳定性。
The major aim of this study was to identify an efficient tool to adjust drug release patterns from aqueous and organic ethylcellulose (a gastrointestinal insoluble polymer) coated pellets and to evaluate the long term stability of the film coatings. Drug release was monitored during open and closed storage at 25°C/60% RH (ambient conditions) and 40°C/75% RH (stress conditions) for up to 24 months. Release of vatalanib succinate, a poorly soluble drug that demonstrates pH-dependent solubility, from pure ethylcellulose coated pellets was slow irrespectively of the type of coating and release medium. By addition of the enteric polymer methacrylic acid/ethyl acrylate copolymer (applied as aqueous Kollicoat MAE 30 DP dispersion or organic solution of Kollicoat MAE 100 P) to ethylcellulose broad ranges of drug release patterns could be achieved. For aqueous film coatings the addition of Kollicoat MAE 30 DP to ethylcellulose dispersions resulted in unaltered drug release kinetics during closed storage at ambient and stress conditions. The storage stabilizing effect of the added enteric polymer might be explained by the more hydrophilic nature of Kollicoat MAE 30 DP compared to ethylcellulose trapping water during film formation and improving polymer particle coalescence. However, during open storage of aqueous coated ethylcellulose:Kollicoat MAE 30 DP pellets at stress conditions drug release decreased due to further gradual polymer particle coalescence. In contrast, drug release rates from organic coated ethylcellulose:Kollicoat MAE 100 P pellets stored at ambient and stress conditions did not change which could be explained by differences in the film formation process. This clearly indicates that the presented concept of the addition of methacrylic acid/ethyl acrylate copolymer to ethylcellulose film coatings in combination with an organic coating process is able to achieve broad ranges of drug release patterns and to overcome storage instability.