Particle-based coarse-grained approach for simulating dry powder inhaler.
Particle-based coarse-grained approach for simulating dry powder inhaler.
复制标题
用于模拟干粉吸入器的基于粒子的粗粒度方法。
DOI：
10.1016/j.ijpharm.2021.120821
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发表时间：
2021
影响因子：
5.8
通讯作者：
Sundaresan,Sankaran
中科院分区：
文献类型：
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作者：
Liu,Xiaoyu;Sulaiman,Mostafa;Kolehmainen,Jari;Ozel,Ali;Sundaresan,Sankaran
通过干粉吸入器 (DPI) 的药物输送是一个复杂的过程，受涉及气体和颗粒的多种因素影响。基于载体的制剂的性能取决于活性药物成分（API）颗粒的释放，通常以细颗粒部分（FPF）和分散部分（DF）为特征。计算流体动力学与离散元法 (CFD-DEM) 相结合可以捕获相关的气体和颗粒相互作用，但计算成本较高，尤其是在跟踪所有载体和 API 颗粒时。本研究通过高分辨率 CFD-DEM 模拟评估了两种粗粒度 CFD-DEM 方法（离散地块方法和代表性粒子方法）的功效。代表性粒子方法模拟所有载体粒子和 API 粒子的子集，而离散地块方法则跟踪代表指定数量的载体或 API 粒子的地块。这两种方法对于需要适度粗粒度的小载体-API 尺寸比都是可行的，但是离散包裹方法显示出对于大载体-API 尺寸比的限制。当模拟每个载体至少包含 10 个代表性 API 颗粒时，代表性颗粒方法可以以合理的精度近似 CFD-DEM 结果。使用代表性颗粒方法，我们探讨了模型问题中可能影响 FPF 和 DF 的粉末特性，并将这些分数与每单位质量 API 颗粒的最大载体-API 内聚力相关联。
Drug delivery via dry powder inhaler (DPI) is a complex process affected by multiple factors involving gas and particles. The performance of a carrier-based formulation depends on the release of active pharmaceutical ingredient (API) particles, typically characterized by fine particle fraction (FPF) and dispersion fraction (DF). Computational Fluid Dynamics coupled with Discrete Element Method (CFD-DEM) can capture relevant gas and particle interactions but is computationally expensive, especially when tracking all carrier and API particles. This study assessed the efficacy of two coarse-grained CFD-DEM approaches, the Discrete Parcel Method and the representative particle approach, through highly-resolved CFD-DEM simulations. The representative particle approach simulates all carrier particles and a subset of API particles, whereas the Discrete Parcel Method tracks parcels representing a specified number of carrier or API particles. Both approaches are viable for a small carrier-API size ratio which requires modest degrees of coarse-graining, but the Discrete Parcel Method showed limitations for a large carrier-API size ratio. The representative particle approach can approximate CFD-DEM results with reasonable accuracies when simulations include at least 10 representative API particles per carrier. Using the representative particle approach, we probed powder characteristics that could affect FPF and DF in a model problem and correlated these fractions with the maximum carrier-API cohesive force per unit mass of API particles.