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Turbuhaler®吸嘴和室对仅含 API 粉体配方气溶胶化的影响。

Effects of the mouthpiece and chamber of Turbuhaler® on the aerosolization of API-only powder formulations.

机构信息

School of Materials Science and Engineering, UNSW Sydney, NSW 2052, Australia.

Advanced Drug Delivery Group, Sydney Pharmacy School, The University of Sydney, NSW 2006, Australia.

出版信息

Int J Pharm. 2023 Apr 25;637:122871. doi: 10.1016/j.ijpharm.2023.122871. Epub 2023 Mar 21.

Abstract

Powder dispersion in dry powder inhalers (DPIs) is affected by powder formulations as well as the design of a device. This paper conducted a numerical investigation based on the coupled computational fluid dynamics (CFD) and discrete element method (DEM) to evaluate the changes of the design of a commercial DPI device Turbuhaler® on the aerosolization of an API-only formulation. Six different designs were proposed by modifying the mouthpiece and chamber of the original geometry which was reconstructed from a CT-scan of the Turbuhaler, and their performances in terms of powder deposition in the device and fine powder fraction (FPF) were evaluated. The resistance of the device was observed to vary with different designs. For the change of the mouthpiece, the device with a cylindrical mouthpiece had the least resistance and the lowest FPF emitted among all the devices, confirming the important role of the spiral mouthpiece on powder dispersion. Reducing the mouthpiece size caused more powder deposition in the inhaler due to higher airflow velocity, but FPF emitted increased compared to the original design as more powder dispersion occurred inside the mouthpiece. The half-length mouthpiece design reduced device resistance to increase airflow velocity and average collision energy, resulting in an increase in FPF loaded but a decrease in the number of collisions. For the change of the chamber, the domed chamber design increased the powder dispersion time and thus enhanced the frequency and energy of particle collisions, which eventually led to an increase in FPF loaded. At fixed flow rates, the powder dispersion efficiency was a function of the device resistance with higher device resistance causing an increase in the FPF loaded. However, it is important for the patient's attainable pressure drop to be considered in this context. Correlations between the aerosolization efficiency and the ratio of the average collision energy and cohesion energy were established based on model-predicted quantities.

摘要

干粉吸入器(DPI)中的粉末分散受粉末配方和设备设计的影响。本文基于计算流体动力学(CFD)和离散元法(DEM)的耦合进行了数值研究,以评估商业 DPI 装置 Turbuhaler®的设计变化对仅 API 配方气溶胶化的影响。通过修改原始几何形状的吸嘴和腔室,提出了六种不同的设计,原始几何形状是根据 Turbuhaler 的 CT 扫描重建的,评估了它们在设备中粉末沉积和细粉分数(FPF)方面的性能。观察到设备阻力随不同设计而变化。对于吸嘴的变化,圆柱形吸嘴的装置阻力最小,发射的 FPF 最低,这证实了螺旋吸嘴对粉末分散的重要作用。减小吸嘴尺寸会由于更高的气流速度而导致设备中沉积更多的粉末,但与原始设计相比,由于更多的粉末在吸嘴内分散,发射的 FPF 增加。半长吸嘴设计降低了设备阻力,增加了气流速度和平均碰撞能,导致加载的 FPF 增加,但碰撞次数减少。对于腔室的变化,圆顶腔室设计增加了粉末分散时间,从而增加了颗粒碰撞的频率和能量,最终导致加载的 FPF 增加。在固定流量下,粉末分散效率是设备阻力的函数,较高的设备阻力会导致加载的 FPF 增加。然而,在这种情况下,考虑患者可达到的压力降很重要。基于模型预测的量,建立了气溶胶化效率与平均碰撞能与内聚能之比之间的相关性。

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