PDF(Pubmed)
Abstract：
In order to achieve the optimal level of effectiveness and safety of drugs, it is necessary to control the drug release rate. Therefore, it is important to discover the factors affecting release profile from a drug delivery system. Geometry is one of these effective factors for a tablet-shaped drug delivery system. In this study, an attempt has been made to answer a general question of how the geometry of a tablet can affect the drug release profile. For this purpose, the drug release process of theophylline from two hundred HPMC-based tablets, which are categorized into eight groups of common geometries in the production of oral tablets, was simulated using finite element analysis. The analysis of the results of these simulations was carried out using statistical methods including partial least squares regression and ANOVA tests. The results showed that it is possible to predict the drug release profile by knowing the geometry type and dimensions of a tablet without performing numerous dissolution tests. Another result was that, although in many previous studies the difference in the drug release profile from several tablets with different geometries was interpreted only by variables related to the surface, the results showed that regardless of the type of geometry and its dimensions, it is not possible to have an accurate prediction of the drug release profile. Also, the results showed that without any change in the dose of the drug and the ingredients of the tablet and only because of the difference in geometry type, the tablets significantly differ in release profile. This occurred in such a way that, for example, the release time of the entire drug mass from two tablets with the same mass and materials but different geometries can be different by about seven times.
摘要：
为了使药物的有效性和安全性达到最佳水平，有必要控制药物释放速率。因此,重要的是发现影响药物递送系统释放曲线的因素。几何形状是片剂形药物递送系统的这些有效因素之一。在这项研究中,已经尝试回答片剂的几何形状如何影响药物释放曲线的一般问题。为此,茶碱从两百片HPMC片剂中的药物释放过程，在口服片剂的生产中被分为八组常见的几何形状，使用有限元分析进行了模拟。使用包括偏最小二乘回归和ANOVA检验的统计方法进行这些模拟结果的分析。结果表明，可以通过了解片剂的几何类型和尺寸来预测药物释放曲线，而无需进行大量的溶出测试。另一个结果是，尽管在许多先前的研究中，几种具有不同几何形状的片剂的药物释放曲线的差异仅通过与表面相关的变量来解释，结果表明，无论几何形状的类型和尺寸如何，不可能准确预测药物释放曲线。此外，结果表明，药物的剂量和片剂的成分没有任何变化，只是因为几何类型的差异，片剂的释放曲线显着不同。这发生在这样一种方式，例如,从具有相同质量和材料但不同几何形状的两个片剂中整个药物质量的释放时间可以相差约7倍。
