Modeling film-coat non-uniformity in polymer coated pellets: a stochastic approach.
Modeling film-coat non-uniformity in polymer coated pellets: a stochastic approach.
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DOI：
10.1016/j.ijpharm.2006.05.064
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发表时间：
2006-10
影响因子：
5.8
通讯作者：
N. Haddish-Berhane;S. Jeong;K. Haghighi;Kinam Park
中科院分区：
文献类型：
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作者：
N. Haddish-Berhane;S. Jeong;K. Haghighi;Kinam Park
本研究的目的是包括涂层厚度的不均匀性的药物释放模型的开发，通过使用随机方法使用涂层离子交换丸。使用能斯特普朗克模型描述从离子交换树脂的药物释放。使用改进的分批方法制备模型药物（美沙芬）和Dowex® 50 WX 4 -200的复合物，并用Kollicoat®SR 30 D聚合物包衣。确定性模型，使用实验药物释放曲线在0%，10%，15%，20%（w/w）的不同涂层厚度进行验证，与实验数据一致，最大均方根误差（RMSE）为2.4%。采用任意拉格朗日-欧拉方法建立了具有非均匀涂层厚度的球形颗粒模型。采用Monte Carlo方法模拟包衣变形程度对累积药物释放曲线的影响。考虑到一个批次中变形和未变形微丸的百分比相等，由于包衣不均匀性，累积释放曲线可能变化约±6%。具有实际不均匀包衣曲线的任意微丸模型获得的释放曲线与理论随机变形微丸模型的平均释放曲线非常一致。所建立的数学模型为评价和预测聚合物涂层离子交换树脂复合物的释放曲线提供了一个有用的工具。
The objective of the present study is to include coating thickness non-uniformity in the development of a drug release model using coated ion-exchange pellets through the use of stochastic approaches. Drug release from ion-exchange resins was described using a Nernst–Plank model. Complexes of a model drug (dextromethorphan) and Dowex®50WX4-200 were prepared using a modified batch method and coated with Kollicoat®SR 30D polymer. The deterministic model, validated using experimental drug release profiles for different coating thicknesses at 0%, 10%, 15%, 20% (w/w), was in agreement with the experimental data with a maximum root mean square error (RMSE) of 2.4%. An arbitrary Lagrangian–Eulerian approach was pursued to develop models of spherical pellets with non-uniform coating thicknesses. The Monte Carlo method was used to simulate the effect of the level of coating deformity on the cumulative drug release profile. Considering the co-existence of equal percentages of deformed and undeformed pellets in a batch, the cumulative release profile can vary by approximately ±6% as a result of coating non-uniformity. The release profile obtained for a model of an arbitrary pellet with an actual non-uniform coating profile was in good agreement with the average release profile for the models of the theoretical randomly deformed pellets. The developed mathematical model is a useful tool to evaluate and predict release profiles of polymer coated ion-exchange resin complexes.