European Egyptian Pharmaceutical Industries, Alexandria, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, El-Khartoum Square, El-Azarita, Alexandria, 21521, Egypt.
AAPS PharmSciTech. 2018 Feb;19(2):912-922. doi: 10.1208/s12249-017-0898-7. Epub 2017 Oct 23.
The permeability of a powder bed reflects its particle size distribution, shape, packing, porosity, cohesivity, and tensile strength in a manner relevant to powder fluidization. The relationship between the permeability and the performance of carrier-based dry powder inhalation (DPI) mixtures has, however, aroused controversy. The current study sought to gain new insights into the relationship and to explore its potential applications. We studied eight lactose materials as DPI carriers. The carriers covered a broad permeability range of 0.42-13.53 D and moreover differed in particle size distribution, particle shape, crystal form, and/or porosity. We evaluated the performance of inhalation mixtures of each of these carriers and fluticasone propionate after aerosolization from an Aerolizer®, a model turbulent-shear inhaler, at a flow rate of 60 L/min. Starting from the high permeability side, the inhalation mixture performance increased as the carrier permeability decreased until optimum performance was reached at permeability of ~ 3.2 D. Increased resistance to air flow strengthens aerodynamic dispersion forces. The inhalation mixture performance then decreased as the carrier permeability further decreased. Very high resistance to air flow restricts powder dispersion. The permeability accounted for effects of carrier size, shape, and macroporosity on the performance. We confirmed the relationship by analysis of two literature permeability-performance datasets, representing measurements that differ from ours in terms of carrier grades, drug, technique used to determine permeability, turbulent-shear inhaler, and/or aerosolization flow rate. Permeability provides useful information that can aid development of DPI mixtures for turbulent-shear inhalers. A practical guidance is provided.
粉末床的渗透性以与粉末流化相关的方式反映其粒径分布、形状、填充、孔隙率、内聚性和拉伸强度。然而，载体型干粉吸入（DPI）混合物的渗透性与性能之间的关系引起了争议。本研究旨在深入了解这种关系，并探索其潜在应用。我们研究了作为 DPI 载体的八种乳糖材料。这些载体的渗透性范围很广，为 0.42-13.53D，此外，它们在粒径分布、颗粒形状、晶体形态和/或孔隙率方面存在差异。我们评估了这些载体中的每一种以及在 60L/min 流速下从 Aerolizer®（一种湍流剪切吸入器）雾化的丙酸氟替卡松的吸入混合物的性能。从高渗透性方面开始，随着载体渗透性的降低，吸入混合物的性能增加，直到渗透性达到约 3.2D 时达到最佳性能。增加对气流的阻力会增强空气动力学分散力。然后，随着载体渗透性的进一步降低，吸入混合物的性能下降。对气流的极高阻力会限制粉末的分散。渗透性解释了载体大小、形状和大孔率对性能的影响。我们通过分析两个文献渗透性-性能数据集证实了这种关系，这两个数据集在载体等级、药物、用于确定渗透性的技术、湍流剪切吸入器和/或雾化流速方面与我们的测量结果不同。渗透性提供了有用的信息，可以帮助开发用于湍流剪切吸入器的 DPI 混合物。提供了实用的指导。
