目的 研究不同分散機(jī)制的粉霧劑裝置氣流阻力與載體型制劑粉末分散行為間的關(guān)系。方法 以Lactohale 206^®與馬來酸氯苯那敏（CPM）混合粉末為制劑模型，4款不同阻力的吸入器為吸入裝置： RS01-L、RS01-M、RS01-H、Handihaler^®（HD），借助計算流體力學(xué)（CFD）、離散相（DPM）、離散元（DEM）方法，探討在30、60 L/min 2種體積流量下，制劑載體顆粒在不同阻力裝置內(nèi)的運動、分散情況；同時，運用新一代撞擊器（NGI）研究模型制劑在2種體積流量下、通過不同裝置后的體外沉積表現(xiàn)，并與數(shù)值模擬結(jié)果進(jìn)行比較、分析。結(jié)果 CFD結(jié)果表明，裝置氣流阻力及氣流流量均對裝置內(nèi)流場強(qiáng)度有影響，當(dāng)裝置內(nèi)體積流量提高時，結(jié)構(gòu)類似的RS01-L、RS01-H的裝置湍流動能變化集中于旋轉(zhuǎn)腔及格柵處區(qū)域，可能會影響膠囊從裝置中的遞送；而HD裝置膠囊倉吸嘴等部件流場紊亂程度均提高。DPM結(jié)果表明，載體顆粒在裝置內(nèi)的運動速度隨裝置阻力及流量提高而增加，對RS01-L、RS01-H類結(jié)構(gòu)而言，流量提高主要促進(jìn)載體在分散腔內(nèi)的運動速度，增加顆粒與裝置的碰撞次數(shù)；HD裝置內(nèi)載體顆粒流量雖提高，但顆粒運動軌跡差異不明顯；DEM結(jié)果表明，相同體積流量下，RS01系列的L、H裝置氣流-顆粒相對速度平方值遠(yuǎn)低于HD裝置，HD裝置中氣流剪切作用強(qiáng)于同等體積流量下RS01裝置，HD裝置總碰撞能量損失遠(yuǎn)低于RS01。體外實驗結(jié)果表明，RS01系列的L、M、H裝置遞送劑量（DD）受體積流量影響較小；HD裝置內(nèi)體積流量越高，裝置殘留和膠囊殘留越低，DD越大；裝置殘留RS01系列明顯高于HD，且隨氣流體積流量的升高，L、M裝置殘留降低顯著（P<0.05、0.001）；HD裝置體積流量提高后，預(yù)分離器藥物殘留顯著降低（P<0.001），但顆粒在慣性作用下在喉管的殘留則顯著增加（P<0.001）；RS01系列裝置在2種體積流量下喉部沉積無顯著性差異，高流量下H裝置預(yù)分離器沉積較低流速顯著增加（P<0.001）；2種體積流量下，微細(xì)粒子劑量（FPD）均隨RS01系列裝置阻力增加而顯著提高（P<0.05、0.01、0.001），質(zhì)量中值空氣動力學(xué)粒徑（MMAD）均隨裝置阻力增加呈下降趨勢；RS01系列裝置分散藥物能力隨體積流量增高而顯著提高（P<0.001）；而對HD裝置而言，體積流量增加后，MMAD雖降低，分散能力有所提升，但FPD變化不明顯。結(jié)論 裝置氣流阻力是調(diào)節(jié)裝置分散性能的一種可行的方式，體積流量一致時，裝置阻力增加（通常由截面積變小造成），氣流流速提高，制劑粉末顆粒運動速度升高，顆粒與裝置壁面的碰撞作用增強(qiáng)，粉末分散效果得到提升，從而改善了藥物分散、沉積表現(xiàn)。

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.