目的 研究不同分散机制的粉雾剂装置气流阻力与载体型制剂粉末分散行为间的关系。方法 以Lactohale 206^®与马来酸氯苯那敏（CPM）混合粉末为制剂模型，4款不同阻力的吸入器为吸入装置： RS01-L、RS01-M、RS01-H、Handihaler^®（HD），借助计算流体力学（CFD）、离散相（DPM）、离散元（DEM）方法，探讨在30、60 L/min 2种体积流量下，制剂载体颗粒在不同阻力装置内的运动、分散情况；同时，运用新一代撞击器（NGI）研究模型制剂在2种体积流量下、通过不同装置后的体外沉积表现，并与数值模拟结果进行比较、分析。结果 CFD结果表明，装置气流阻力及气流流量均对装置内流场强度有影响，当装置内体积流量提高时，结构类似的RS01-L、RS01-H的装置湍流动能变化集中于旋转腔及格栅处区域，可能会影响胶囊从装置中的递送；而HD装置胶囊仓吸嘴等部件流场紊乱程度均提高。DPM结果表明，载体颗粒在装置内的运动速度随装置阻力及流量提高而增加，对RS01-L、RS01-H类结构而言，流量提高主要促进载体在分散腔内的运动速度，增加颗粒与装置的碰撞次数；HD装置内载体颗粒流量虽提高，但颗粒运动轨迹差异不明显；DEM结果表明，相同体积流量下，RS01系列的L、H装置气流-颗粒相对速度平方值远低于HD装置，HD装置中气流剪切作用强于同等体积流量下RS01装置，HD装置总碰撞能量损失远低于RS01。体外实验结果表明，RS01系列的L、M、H装置递送剂量（DD）受体积流量影响较小；HD装置内体积流量越高，装置残留和胶囊残留越低，DD越大；装置残留RS01系列明显高于HD，且随气流体积流量的升高，L、M装置残留降低显著（P<0.05、0.001）；HD装置体积流量提高后，预分离器药物残留显著降低（P<0.001），但颗粒在惯性作用下在喉管的残留则显著增加（P<0.001）；RS01系列装置在2种体积流量下喉部沉积无显著性差异，高流量下H装置预分离器沉积较低流速显著增加（P<0.001）；2种体积流量下，微细粒子剂量（FPD）均随RS01系列装置阻力增加而显著提高（P<0.05、0.01、0.001），质量中值空气动力学粒径（MMAD）均随装置阻力增加呈下降趋势；RS01系列装置分散药物能力随体积流量增高而显著提高（P<0.001）；而对HD装置而言，体积流量增加后，MMAD虽降低，分散能力有所提升，但FPD变化不明显。结论 装置气流阻力是调节装置分散性能的一种可行的方式，体积流量一致时，装置阻力增加（通常由截面积变小造成），气流流速提高，制剂粉末颗粒运动速度升高，颗粒与装置壁面的碰撞作用增强，粉末分散效果得到提升，从而改善了药物分散、沉积表现。

Objective To study the relationship between airflow resistance of dry powder inhaler devices with different dispersion mechanisms and the dispersion behaviors of carrier-type formulation. Methods A mixture of carrier lactose (Lactohale206^®) and micronized chlorphenamine maleate (CPM) was used as the preparation model and four inhalers (RS01-L, RS01-M, RS01-H, Handihaler^®) with different resistance were used as the inhalation device. The influence of the airflow resistance on the flow field and dispersion process of particles were collected and analyzed by Computational Fluid Dynamics (CFD), Discrete Phase Method (DPM) and discrete element method (DEM). The next generation pharmaceutical impactor (NCI) was used to evaluate the in vitro deposition performance of the formulation model with four inhalation devices at two flow rates at the same time. Then the in-vitro results were compared and analyzed with the numerical simulation results. Results The CFD results showed that both the airflow resistance and flow rate of the device had an effect on the intensity of the flow field in the device. When the volume flow rate in the device increased, the turbulence kinetic energy of the device with similar structure RS01-L and RS01-H concentrates on the region of the rotating cavity and the grating, which may affect the delivery of the capsule from the device. However, the flow field disturbance of the capsule capsule nozzle and other components of HD device was increased. The DPM results show that the velocity of the carrier particles in the device increased with the increase of the device resistance and flow rate. For RS01-L and RS01-H structures, the increase of flow rate mainly improved the velocity of the carrier in the dispersion cavity and increased the number of collisions between the particles and the device. Although the flow rate of carrier particles in the HD device increased, the difference of particle trajectory was not obvious. DEM results showed that the square value of airflow-particle relative velocity of L and H device of RS01 series was much lower than that of HD device at the same volume flow rate, the shear effect of airflow in HD device was stronger than that of RS01 device at the same volume flow rate, and the total impact energy loss of HD device was much lower than that of RS01 device. The results of in vitro experiments showed that the delivery dose (DD) of L, M and H devices of RS01 series was less affected by the volume flow. The higher the volume flow in HD device, the lower the device residue and capsule residue, and the higher the DD. The device residual RS01 series was significantly higher than HD, and with the increase of the volume flow rate, the device residual of L and M was significantly decreased (P < 0.05, 0.001). After the volume flow of HD device increased, the drug residue in the preseparator was significantly decreased (P < 0.001), but the particle residue in the throat under the inertial action was significantly increased (P < 0.001). There was no significant difference in throat deposition of RS01 series devices under two kinds of volume flow rates. At high flow rate, the deposition of preseparator of H device increased significantly compared with low flow rate (P < 0.001). Under the two kinds of volume flow, the dose of fine particles (FPD) was significantly increased with the increase of resistance of RS01 series devices (P < 0.05, 0.01, 0.001), and the median aerodynamic particle size (MMAD) showed a downward trend with the increase of resistance. The drug dispersing capacity of RS01 series devices was significantly increased with the increase of volume flow (P < 0.001). For HD devices, with the increase of volumetric flow, the MMAD decreased and the dispersion increased, but the FPD did not change significantly. Based on the formulation model, the variation trend of fine particle dose (FPD) is consistent with the relative velocity of particle-air flow, that is, with the increase of relative velocity, the shear force of air flow increases, and FPD shows an upward trend. Conclusion Within the scope of this experiment, the in vitro deposition performance increases significantly with the increase of device resistance, which indicates that it's a feasible way to improve the dispersion performance by adjusting the airflow resistance of the inhalation device. When the volume flow rate is consistent, the resistance of the device increases (usually caused by the decrease of the cross-sectional area) leads to the increases airflow velocity and the movement speed of preparation powder particles, the collision between the particles and the device wall is also enhanced, which advances the degree of powder dispersion and thereby improvs the drug dispersion and deposition performance.