Towards quantitative prediction of the performance of dry powder inhalers by multi-scale simulations and experiments
Towards quantitative prediction of the performance of dry powder inhalers by multi-scale simulations and experiments
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DOI：
10.1016/j.ijpharm.2018.05.047
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发表时间：
2018-08-25
影响因子：
5.8
通讯作者：
Thalberg, Kyrre
中科院分区：
文献类型：
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作者：
Duy Nguyen;Remmelgas, Johan;Thalberg, Kyrre
这项工作展示了使用多尺度模拟与实验相结合来建立干粉吸入器（DPI）中粘合剂混合物性能的定量预测工具。使用离散元模型（DEM），细载流子粒子在剂量夹带和分散过程中遇到的不同机制上的行为可以在单个粒子水平上描述。将这些结果与计算流体动力学（CFD）模拟相结合，可以捕获DPI的完整剂量事件，并提取关键性能指标。引入了表观表面能（ASE）的概念，以克服与复杂颗粒性质相关的挑战，例如不规则颗粒形状和表面粗糙度。这种方法正确地预测了实验中观察到的API粘附性、流速和设备几何形状的趋势。通过将药物负荷、临界黏附和表面能分布的影响结合到模拟工具中，可以预测两种不同配方在两种不同流速下的细颗粒分数，与实验结果非常吻合。结论是，多尺度模拟为支持器件和配方的开发提供了有用的工具，并进一步了解控制dpi分散的物理机制。
This work demonstrates the use of multi-scale simulations coupled with experiments to build a quantitative prediction tool for the performance of adhesive mixtures in a dry powder inhaler (DPI). Using discrete element model (DEM), the behaviour of fine-carrier particle assemblies upon different mechanisms encountered during dose entrainment and dispersion can be described at the individual particle level. Combining these results with computational fluid dynamics (CFD) simulations, the complete dosing event from a DPI can be captured and key performance measures can be extracted. A concept of apparent surface energy, ASE, was introduced to overcome challenges associated with the complex particle properties, e.g. irregular particle shapes and surface roughness. This approach correctly predicts trends observed experimentally regarding API adhesivity, flow rate and device geometry. By incorporating the effects of drug load, critical adhesion and surface energy distributions to the simulation tool, the fine particle fraction could be predicted with good agreement to experiments for two different formulations in two different devices at two flow rates. It is concluded that multi-scale simulations provide a useful tool to support device and formulation development, as well as to gain further insight into the physical mechanisms governing dispersion from DPIs.