Division of Drugs, National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki-Ku, Kawasaki, Kanagawa, 210-9501, Japan.
Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
AAPS PharmSciTech. 2024 Oct 22;25(8):251. doi: 10.1208/s12249-024-02972-x.
The effects of glass bead size in the conical space of flow-through cells on the dissolution profiles were investigated in a USP apparatus 4. Dissolution tests of disintegrating and non-disintegrating tablets in flow-through dissolution systems were performed using semi-high precision glass beads with diameters ranging from 0.5 mm to 1.5 mm. Computational fluid dynamics (CFD) was used to evaluate the effect of shear stress from the dissolution media flow. The use of smaller glass beads in a larger cell resulted in a faster dissolution of the model formulations under certain test conditions. The effect on the dissolution was highly dependent on the size of the beads in the top layer, including those in contact with the tablets. The absence of a bead-size effect on the dissolution of an orodispersible tablet in a small cell can be explained by the floating fragments during the test. CFD analysis showed that smaller bead diameters led to greater shear stress on the tablet, which was correlated with the dissolution rate. Hence, fluid flow through the narrow gaps between the small beads generated strong local flows, causing shear stress. The size of the glass beads used in flow-through cells affects the dissolution rate of tablets by altering the shear stress on the tablets in certain cases (e.g., direct deposition of the formulation on glass beads, large cells, and very low flow rates). Thus, glass bead size must be considered for a robust dissolution test in a flow-through cell system.
在 USP 仪器 4 中研究了在流动池的锥形空间中玻璃珠大小对溶解曲线的影响。使用直径为 0.5-1.5mm 的半高精度玻璃珠在流动溶解系统中对可崩解和不可崩解片剂进行了溶解测试。计算流体动力学（CFD）用于评估溶解介质流动产生的剪切应力的影响。在某些测试条件下，在较大的池内使用较小的玻璃珠可使模型配方更快地溶解。对溶解的影响高度取决于顶层（包括与片剂接触的）玻璃珠的大小。在小池中的分散片的溶解不受珠粒尺寸影响，这可以通过测试过程中的漂浮碎片来解释。CFD 分析表明，较小的珠粒直径会导致片剂上的剪切应力更大，这与溶解速率相关。因此，通过小玻璃珠之间的狭窄间隙的流体流动产生了强大的局部流动，从而产生了剪切应力。在某些情况下（例如，制剂直接沉积在玻璃珠上、大池和非常低的流速），流动池内使用的玻璃珠的大小会通过改变片剂上的剪切应力来影响片剂的溶解速率。因此，在流动池系统中进行稳健的溶解测试时，必须考虑玻璃珠的大小。
