Telko M J, Hickey A J
Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599-7571, USA,
AAPS PharmSciTech. 2014 Dec;15(6):1378-97. doi: 10.1208/s12249-014-0144-5. Epub 2014 Jun 18.
The impact of formulation variables on aerodynamic and electrostatic properties of dry powder aerosol particles is of great importance to the development of efficient and reproducible inhaler products. Systematic evaluation requires a well-designed series of experiments using appropriate methods. A factorial experimental design was employed. In broad terms, the conditions considered were two drugs, albuterol and budesonide, in combination with different excipients, drug concentrations, delivered doses, and metering system (capsule composition) and sampled under different flow conditions using standard entrainment tubes. Samples were collected in an electrical low-pressure impactor, to evaluate distribution of electrostatic properties, and an Andersen eight-stage nonviable cascade impactor, to estimate aerodynamic particle size distribution, concurrently. The deposition studies allowed calculation of approximate per particle charge levels for drug. The results showed very high particle charge levels, often in the 1,000-10,000 of elementary charges per particle range, orders of magnitude higher than charge levels predicted by the Boltzmann charge distribution. The charge levels are considerably higher than had previously been estimated (200e per particle).
制剂变量对干粉气雾剂颗粒的空气动力学和静电特性的影响对于高效且可重复的吸入器产品的开发至关重要。系统评估需要使用适当方法进行精心设计的一系列实验。采用了析因实验设计。大体而言，所考虑的条件包括两种药物，即沙丁胺醇和布地奈德，与不同的辅料、药物浓度、给药剂量以及计量系统（胶囊组成）相结合，并在不同流动条件下使用标准夹带管进行采样。同时在一个用于评估静电特性分布的低压电冲击器和一个用于估计空气动力学粒径分布的安德森八级非活性级联冲击器中收集样品。沉积研究使得能够计算药物的近似单颗粒电荷水平。结果显示颗粒电荷水平非常高，通常在每颗粒1000 - 10000个基本电荷的范围内，比玻尔兹曼电荷分布预测的电荷水平高几个数量级。这些电荷水平比之前估计的（每颗粒约200e）要高得多。
