School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Respirent Pharmaceuticals Co., Ltd, Chongqing 400714, China.
Int J Pharm. 2020 Feb 15;575:119000. doi: 10.1016/j.ijpharm.2019.119000. Epub 2019 Dec 29.
Based on dry powder inhaler (DPI) inhalation process, powder properties have a key influence on fluidization and deagglomeration behavior during aerosol generation. The aim of this study was to explore the influence of drug content on DPI powder properties and further reveal the correlations between powder properties and pulmonary deposition efficiency. Using salbutamol sulfate as a model drug, Lactohale® 100 as carrier, carrier-based binary mixtures were prepared at drug content from 0.5 to 10% (w/w), characterized with powder rheometer, faraday cage and Next Generation Impactor. It was demonstrated that drug content had a remarkable influence on powder behavior, and good correlations between powder properties and fine particle fraction (FPF) were established in drug content range 0.5-7%. A negative correlation between basic flowability energy and FPF, reflected a good flowability is beneficial for powder fluidization. Further properties characterization, including aeration ratio, permeability, pre-shear stress and aerodynamic specific charge, suggested a strong interaction is beneficial for powder deagglomeration. It's the first time that interaction indicator and flowability indicator were extracted with principal component analysis (PCA). In conclusion, drug content has a significant influence on powder properties. DPI formulations with a stronger interaction and meanwhile a better flowability are desirable for enhanced pulmonary drug delivery.
基于干粉吸入器（DPI）的吸入过程，粉末特性对气溶胶生成过程中的流化和团聚体解聚行为有重要影响。本研究旨在探讨药物含量对 DPI 粉末特性的影响，并进一步揭示粉末特性与肺部沉积效率之间的相关性。以硫酸沙丁胺醇为模型药物，以 Lactohale®100 为载体，制备了药物含量从 0.5%到 10%（w/w）的载体制备二元混合物，采用粉末流变仪、法拉第笼和下一代撞击器进行了表征。结果表明，药物含量对粉末行为有显著影响，在 0.5%至 7%的药物含量范围内，建立了粉末特性与细颗粒分数（FPF）之间的良好相关性。基本流动性能量与 FPF 之间呈负相关，表明良好的流动性有利于粉末的流化。进一步的特性表征，包括通气比、渗透率、预剪切应力和空气动力学比电荷，表明强相互作用有利于粉末解团聚。这是首次采用主成分分析（PCA）提取相互作用指标和流动性指标。总之，药物含量对粉末特性有显著影响。对于增强肺部药物输送，具有更强相互作用同时具有更好流动性的 DPI 配方是理想的。
