Institute of Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13, 8010 Graz, Austria; Research Center Pharmaceutical Engineering, Inffeldgasse 13, 8010 Graz, Austria.
Institute of Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13, 8010 Graz, Austria; Research Center Pharmaceutical Engineering, Inffeldgasse 13, 8010 Graz, Austria.
Eur J Pharm Sci. 2022 Jan 1;168:106073. doi: 10.1016/j.ejps.2021.106073. Epub 2021 Nov 11.
The dispersion of carrier-based formulations in capsule-based dry powder inhalers depends on several factors, including the patient's inhalation profile and the motion of capsule within the device. In the present study, coupled computational fluid dynamics and discrete element method simulations of a polydisperse cohesive lactose carrier in an Aerolizer® inhaler were conducted at a constant flow rate of 100 L/min and considering an inhalation profile of asthmatic children between 5 and 17 years approximated from literature data. In relevant high-speed photography experiments, it was observed that the powder was distributed to both capsule ends before being ejected from the capsule. Several methods of ensuring similar behavior in the simulations were presented. Both the constant flow rate simulation and the profile simulations showed a high powder retention in the capsule (7.37-19.00%). Although the inhaler retention was negligible in the constant flow rate simulation due to consistently high air velocities in the device, it reached values of around 7% in most of the profile simulations. In all simulations, some of the carrier powder was ejected from the capsule as particle clusters. These clusters were larger in the profile simulation than in the constant flow rate simulation. Of the powder discharged from the capsule, a high percentage was bound in clusters in the profile simulation in the beginning and at the end of the inhalation profile while no more than 10% of the powder ejected from the capsule in the 100 L/min constant flow rate simulation were in clusters at any time. The powder emission from the capsule was studied, indicating a strong dependency of the powder mass flow from the capsule on the angular capsule position. When the capsule holes face the inhaler's air inlets, the air flow into the capsule restricts the powder discharge. The presented results provide a detailed view of some aspects of the powder flow and dispersion of a cohesive carrier in a capsule-based inhaler device. Furthermore, the importance of considering inhalation profiles in addition to conventional constant flow rate simulations was confirmed.
载药制剂在胶囊型干粉吸入器中的分散取决于多种因素，包括患者的吸入模式和胶囊在装置内的运动。在本研究中，在 100 L/min 的恒定流速下，对 Aerolizer®吸入器中多分散粘性乳糖载体的计算流体动力学和离散元方法模拟进行了模拟，并考虑了从文献数据中近似得出的 5 至 17 岁哮喘儿童的吸入模式。在相关的高速摄影实验中，观察到粉末在从胶囊中喷出之前被分配到胶囊的两端。提出了几种确保模拟中类似行为的方法。恒定流速模拟和模式模拟都显示胶囊内的粉末保留率很高（7.37-19.00%）。尽管由于装置内的空气速度始终很高，在恒定流速模拟中吸入器保留率可以忽略不计，但在大多数模式模拟中，它达到了约 7%的值。在所有模拟中，一些载体粉末作为颗粒簇从胶囊中喷出。这些簇在模式模拟中比在恒定流速模拟中更大。在从胶囊中排出的粉末中，在开始和结束吸入模式时，在 profile 模拟中有很大一部分粉末结合在簇中，而在 100 L/min 恒定流速模拟中，从胶囊中排出的粉末中没有超过 10%的粉末在任何时候都在簇中。研究了从胶囊中排出的粉末，表明从胶囊中排出的粉末质量流强烈依赖于胶囊的角位置。当胶囊孔面向吸入器的空气入口时，进入胶囊的空气流会限制粉末的排出。所提出的结果提供了粘性载体在胶囊型干粉吸入器装置中粉末流动和分散的某些方面的详细视图。此外，还证实了除了常规恒定流速模拟之外，还需要考虑吸入模式的重要性。
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