Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208.
Process Research and Development, AbbVie Inc., North Chicago, Illinois 60064.
J Pharm Sci. 2020 Mar;109(3):1231-1241. doi: 10.1016/j.xphs.2019.11.008. Epub 2019 Nov 16.
Computational fluid dynamics (CFD) has been extensively used for the USP paddle apparatus II, but limited CFD studies have been conducted on the USP basket apparatus I. We expanded on past CFD basket studies to consider the presence of a tablet inside the basket, compared predictions to in vivo conditions, and confirmed observations around the complexity of nonuniform hydrodynamics. Tablets near the basket perimeter experienced near 5-fold increase in maximum velocity and surface shear stress compared to tablets placed at the center of the basket. At higher basket speeds, the predicted velocities at the center of the basket were closer to in vivo predictions but the surface shear stress was about 2 orders of magnitude lesser. Simulations with a high viscosity fluid (1 Pa-s) showed a 10-fold increase in shear stress on a tablet but a decrease in strain rate compared to low-viscosity medium (0.001 Pa-s) which could impact dissolution rates. Also presented are the insights into turbulent energy dissipation rates that could help in a priori prediction of dissolution rates. Overall, the CFD analysis presented in this work reveals significant differences between the basket and in vivo conditions and will help inform relevant in vitro testing.
计算流体动力学（CFD）已广泛应用于 USP 桨式装置 II，但对 USP 篮式装置 I 的 CFD 研究有限。我们在过去的 CFD 篮式研究的基础上进行了扩展，考虑了篮内片剂的存在，将预测值与体内条件进行了比较，并证实了非均匀流体动力学复杂性的观察结果。与放置在篮中心的片剂相比，靠近篮周边的片剂的最大速度和表面剪切应力增加了近 5 倍。在较高的篮速度下，篮中心的预测速度更接近体内预测值，但表面剪切应力小约 2 个数量级。用高粘度流体（1 Pa-s）进行的模拟显示，片剂上的剪切应力增加了 10 倍，但与低粘度介质（0.001 Pa-s）相比，应变速率降低，这可能会影响溶解速率。还介绍了有助于溶解速率先验预测的湍流能量耗散率的见解。总体而言，本文提出的 CFD 分析揭示了篮式装置和体内条件之间的显著差异，并将有助于相关的体外测试。
