Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Int J Pharm. 2012 May 30;428(1-2):57-67. doi: 10.1016/j.ijpharm.2012.02.031. Epub 2012 Feb 28.
The main objective of the study was to develop artificial intelligence methods for optimization of drug release from matrix tablets regardless of the matrix type. Static and dynamic artificial neural networks of the same topology were developed to model dissolution profiles of different matrix tablets types (hydrophilic/lipid) using formulation composition, compression force used for tableting and tablets porosity and tensile strength as input data. Potential application of decision trees in discovering knowledge from experimental data was also investigated. Polyethylene oxide polymer and glyceryl palmitostearate were used as matrix forming materials for hydrophilic and lipid matrix tablets, respectively whereas selected model drugs were diclofenac sodium and caffeine. Matrix tablets were prepared by direct compression method and tested for in vitro dissolution profiles. Optimization of static and dynamic neural networks used for modeling of drug release was performed using Monte Carlo simulations or genetic algorithms optimizer. Decision trees were constructed following discretization of data. Calculated difference (f(1)) and similarity (f(2)) factors for predicted and experimentally obtained dissolution profiles of test matrix tablets formulations indicate that Elman dynamic neural networks as well as decision trees are capable of accurate predictions of both hydrophilic and lipid matrix tablets dissolution profiles. Elman neural networks were compared to most frequently used static network, Multi-layered perceptron, and superiority of Elman networks have been demonstrated. Developed methods allow simple, yet very precise way of drug release predictions for both hydrophilic and lipid matrix tablets having controlled drug release.
本研究的主要目的是开发人工智能方法,以优化无论基质类型如何的药物从基质片中的释放。开发了静态和动态人工神经网络,具有相同的拓扑结构,用于使用配方组成、用于压片的压缩力以及片剂孔隙率和拉伸强度作为输入数据来模拟不同基质片类型(亲水/脂质)的溶出曲线。还研究了决策树在从实验数据中发现知识的潜在应用。聚氧化乙烯聚合物和甘油棕榈硬脂酸酯分别用作亲水和脂质基质片的基质形成材料,而选择的模型药物为双氯芬酸钠和咖啡因。通过直接压缩法制备基质片,并测试体外溶出曲线。使用蒙特卡罗模拟或遗传算法优化器对用于药物释放建模的静态和动态神经网络进行了优化。对数据进行离散化后构建决策树。对于预测和实验获得的测试基质片配方的溶出曲线,计算的差异(f(1))和相似性(f(2))因子表明,Elman 动态神经网络以及决策树能够准确预测亲水和脂质基质片的溶出曲线。将 Elman 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 Elman 网络的优越性。开发的方法允许对具有控制药物释放的亲水和脂质基质片进行简单但非常精确的药物释放预测。