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动态神经网络在聚环氧乙烷基质片剂药物释放建模中的应用。

Application of dynamic neural networks in the modeling of drug release from polyethylene oxide matrix tablets.

作者信息

Petrović Jelena, Ibrić Svetlana, Betz Gabriele, Parojcić Jelena, Durić Zorica

机构信息

Institute of Pharmaceutical Technology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.

出版信息

Eur J Pharm Sci. 2009 Sep 10;38(2):172-80. doi: 10.1016/j.ejps.2009.07.007. Epub 2009 Jul 24.

Abstract

The main objective of this study was to demonstrate the possible use of dynamic neural networks to model diclofenac sodium release from polyethylene oxide hydrophilic matrix tablets. High and low molecular weight polymers in the range of 0.9-5 x 10(6) have been used as matrix forming materials and 12 different formulations were prepared for each polymer. Matrix tablets were made by direct compression method. Fractions of polymer and compression force have been selected as most influential factors on diclofenac sodium release profile. In vitro dissolution profile has been treated as time series using dynamic neural networks. Dynamic networks are expected to be advantageous in the modeling of drug release. Networks of different topologies have been constructed in order to obtain precise prediction of release profiles for test formulations. Short-term and long-term memory structures have been included in the design of network making it possible to treat dissolution profiles as time series. The ability of network to model drug release has been assessed by the determination of correlation between predicted and experimentally obtained data. Calculated difference (f(1)) and similarity (f(2)) factors indicate that dynamic networks are capable of accurate predictions. Dynamic neural networks were compared to most frequently used static network, multi-layered perceptron, and superiority of dynamic networks has been demonstrated. The study also demonstrated differences between the used polyethylene oxide polymers in respect to drug release and suggests explanations for the obtained results.

摘要

本研究的主要目的是证明动态神经网络在模拟双氯芬酸钠从聚环氧乙烷亲水基质片剂中释放方面的可能用途。分子量在0.9 - 5×10(6)范围内的高分子量和低分子量聚合物已被用作基质形成材料,每种聚合物制备了12种不同的配方。基质片剂采用直接压片法制备。聚合物比例和压片力已被选为对双氯芬酸钠释放曲线影响最大的因素。利用动态神经网络将体外溶出曲线作为时间序列进行处理。动态网络有望在药物释放建模中具有优势。构建了不同拓扑结构的网络,以便对测试配方的释放曲线进行精确预测。网络设计中包含了短期和长期记忆结构,使得将溶出曲线作为时间序列处理成为可能。通过确定预测数据与实验获得的数据之间的相关性来评估网络模拟药物释放的能力。计算得到的差异(f(1))和相似性(f(2))因子表明动态网络能够进行准确预测。将动态神经网络与最常用的静态网络——多层感知器进行了比较,证明了动态网络的优越性。该研究还证明了所用聚环氧乙烷聚合物在药物释放方面的差异,并对所得结果提出了解释。

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