Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia.
Pharm Res. 2010 Jul;27(7):1367-76. doi: 10.1007/s11095-010-0128-4. Epub 2010 Apr 6.
This study utilized a combination of computational fluid dynamics (CFD) and standardized entrainment tubes to investigate the influence of turbulence on the break-up and aerosol performance of a model inhalation formulation.
Agglomerates (642.8 mum mean diameter) containing 3.91 mum median diameter primary spherical mannitol particles were prepared by spheronisation. A series of entrainment tubes with different Venturi sections were constructed in silico, and the flow pattern and turbulence/impaction parameters were predicted using CFD. The entrainment models were constructed from the in silico model using three-dimensional printing. The aerosol performance of the mannitol was assessed by entraining the agglomerates into the experimental tubes at a series of flow rates and assessing the size distribution downstream of the venturi via in-line laser diffraction.
A series of parameters (including Reynolds number (Re), turbulence kinetic energy, turbulence eddy frequency, turbulence length-scale, velocity and pressure drop) were calculated from the CFD simulation. The venturi diameter and volumetric flow rate were varied systematically. The particle size data of the agglomerated powders were then correlated with the CFD measurements. No correlation between turbulence and aerosol performance could be made (i.e. at a Reynolds number of 8,570, the d(0.1) was 52.5 mum +/- 19.7 mum, yet at a Reynolds number of 12,000, the d(0.1) was 429.1 mum +/- 14.8 mum). Lagrangian particle tracking indicated an increase in the number of impactions and the normal velocity component at the wall, with increased volumetric airflow and reduced venturi diameter. Chemical analysis of the mannitol deposited on the walls showed a linear relationship with respect to the theoretical number of impactions (R(2) = 0.9620). Analysis of the relationship between the CFD results and the experimental size data indicated a critical impact velocity was required to initiate agglomerate break-up ( approximately 0.4 m.s(-1)).
While this study focussed on the effect of turbulence on agglomerate break-up, the small amount of impaction, which inevitably occurs in the venturi assembly, appeared to dominate agglomerate break-up in this dry powder system.
本研究采用计算流体动力学（CFD）和标准化吸入管相结合的方法，研究了湍流对模型吸入制剂的 breakup 和气溶胶性能的影响。
通过滚圆法制备了含有 3.91 µm 中值直径初级球形甘露醇颗粒的团聚体（642.8 µm 平均直径）。在计算机中构建了一系列具有不同文丘里管段的吸入管，使用 CFD 预测流型和湍流/冲击参数。使用三维打印从计算机模型构建吸入模型。通过在一系列流速下将团聚体吸入实验管中，并通过在线激光衍射评估文丘里管下游的粒径分布，评估甘露醇的气溶胶性能。
从 CFD 模拟中计算了一系列参数（包括雷诺数（Re）、湍流动能、湍流涡频率、湍流长度尺度、速度和压降）。系统地改变了文丘里管的直径和体积流量。然后将团聚粉末的粒径数据与 CFD 测量值相关联。无法将湍流与气溶胶性能进行关联（即雷诺数为 8570 时，d(0.1) 为 52.5 µm ± 19.7 µm，而雷诺数为 12000 时，d(0.1) 为 429.1 µm ± 14.8 µm）。拉格朗日粒子跟踪表明，随着体积气流的增加和文丘里管直径的减小，冲击次数和壁面法向速度分量增加。对沉积在壁上的甘露醇进行化学分析表明，其与理论冲击次数呈线性关系（R²=0.9620）。CFD 结果与实验粒径数据之间关系的分析表明，团聚体 breakup 需要一个临界冲击速度（约 0.4 m.s⁻¹）。
虽然本研究重点关注了湍流对团聚体 breakup 的影响，但在这个干粉系统中，文丘里组件中不可避免地会发生少量的冲击，这似乎主导了团聚体的 breakup。
