A reappraisal of drug release laws using Monte Carlo simulations: The prevalence of the Weibull function
A reappraisal of drug release laws using Monte Carlo simulations: The prevalence of the Weibull function
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DOI：
10.1023/a:1024497920145
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发表时间：
2003-07-01
影响因子：
3.7
通讯作者：
Macheras, P
中科院分区：
文献类型：
--
作者：
Kosmidis, K;Argyrakis, P;Macheras, P
目的.目的验证Higuchi定律，并通过Monte Carlo计算机模拟研究药物从圆柱形和球形骨架中的释放。一个一维矩阵，根据理论假设推导的Higuchi定律，进行了模拟和监测其时间演变。模拟圆柱形和球形三维晶格，其中晶格边界处的位点被表示为泄漏位点。粒子被允许使用随机行走模型在其中移动。假设颗粒之间的体积相互作用被排除在外。我们监测了不同晶格尺寸和不同初始粒子浓度下系统的时间演化。Higuchi定律在一维晶格中用Monte Carlo方法进行了验证。结果发现，从圆柱形矩阵的Fickian药物释放可以很好地近似与威布尔函数。Weibull函数参数与体系比表面积之间存在简单的线性关系。作为扩散过程的结果，假设药物分子之间排除体积相互作用，可以使用威布尔函数描述药物从基质中释放。这个模型，虽然近似和半经验，提供了一个简单的物理连接模型参数和系统的几何形状，这是从其他半经验模型所缺少的东西之间的好处。
Purpose. To verify the Higuchi law and study the drug release from cylindrical and spherical matrices by means of Monte Carlo computer simulation.Methods. A one-dimensional matrix, based on the theoretical assumptions of the derivation of the Higuchi law, was simulated and its time evolution was monitored. Cylindrical and spherical three-dimensional lattices were simulated with sites at the boundary of the lattice having been denoted as leak sites. Particles were allowed to move inside it using the random walk model. Excluded volume interactions between the particles was assumed. We have monitored the system time evolution for different lattice sizes and different initial particle concentrations.Results. The Higuchi law was verified using the Monte Carlo technique in a one-dimensional lattice. It was found that Fickian drug release from cylindrical matrices can be approximated nicely with the Weibull function. A simple linear relation between the Weibull function parameters and the specific surface of the system was found.Conclusions. Drug release from a matrix, as a result of a diffusion process assuming excluded volume interactions between the drug molecules, can be described using a Weibull function. This model, although approximate and semiempirical, has the benefit of providing a simple physical connection between the model parameters and the system geometry, which was something missing from other semiempirical models.