Small Molecule Pharmaceutical Sciences, Genentech, Inc., South San Francisco, CA 94080, United States.
Small Molecule Pharmaceutical Sciences, Genentech, Inc., South San Francisco, CA 94080, United States.
J Pharm Sci. 2021 Nov;110(11):3614-3622. doi: 10.1016/j.xphs.2021.07.001. Epub 2021 Jul 4.
The purpose of the study is to present the finite difference method (FDM) and demonstrate its utility in modeling mass transport processes that are pharmaceutically relevant. In particular, diffusion processes are ideally suited for FDM because the governing equation, Fick's second law of diffusion, can be readily solved using FDM over a finite space and time. The method entails the mesh creation, space and time discretization, and solving Fick's second law at each node using finite difference-based numerical schemes. We applied FDM to study tablet disintegration, in which the tablet water uptake was simulated with an effective water diffusion coefficient; the tablet disintegration was controlled by a designated critical water content parameter, beyond which the node is treated as being disintegrated from the tablet. The resulting simulation agreed with the experimental tablet disintegration behaviors, under both disintegration-controlled and water uptake-controlled conditions. This study highlighted the unique advantage of FDM, capable of providing spatial-temporal information on water uptake and evolution of tablet size and shape during tablet disintegration, which was otherwise not available using other methods. The FDM method enabled more in-depth tablet disintegration studies. The model also has the potential to be calibrated and incorporated in tablet formulation DoE studies.
本研究的目的是介绍有限差分法(FDM),并展示其在建模与药物相关的质量传递过程中的应用。特别是,扩散过程非常适合使用 FDM,因为控制方程——菲克第二扩散定律——可以在有限的空间和时间内使用 FDM 来轻松求解。该方法涉及网格创建、空间和时间离散化,以及在每个节点使用基于有限差分的数值方案求解菲克第二定律。我们应用 FDM 研究了片剂崩解,其中使用有效水扩散系数模拟了片剂的水分吸收;片剂的崩解由指定的临界含水量参数控制,超过该参数的节点被视为从片剂中崩解。在崩解控制和水分吸收控制条件下,所得模拟与实验片剂崩解行为一致。本研究强调了 FDM 的独特优势,它能够提供片剂崩解过程中水分吸收和片剂大小形状演变的时空信息,而其他方法则无法提供这些信息。FDM 方法能够进行更深入的片剂崩解研究。该模型还有望进行校准并纳入片剂配方 DOE 研究。