College of Pharmacy, Université Lille Nord de France, Lille, France.
Eur J Pharm Biopharm. 2010 Nov;76(3):464-9. doi: 10.1016/j.ejpb.2010.09.003. Epub 2010 Sep 18.
Dry Powder Inhalers have drawn great attention from pharmaceutical scientists in recent years in particular those consisting of low-dose micronized drug particles associated with larger carrier particles and called interactive mixtures. However, there is little understanding of the relation between bulk powder properties such as powder structure and its aerodynamic dispersion performance. The aim of this work was to develop a simple method to measure the air permeability of interactive mixtures used in Dry Powder Inhalers by using Blaine's apparatus--a compendial permeameter and to relate it to the aerodynamic behaviour. The study was done with fluticasone propionate and terbutaline sulphate as drug models that were blended with several lactoses having different particle size distribution thus containing different percentages of fine particle lactose. The quality of the blends was examined by analysing the drug content uniformity. Aerodynamic evaluation of fine particle fraction was obtained using a Twin Stage Impinger. A linear correlation between a bulk property--air permeability of packed powder bed--and the fine particle fraction of drug was observed for the tested drugs. The air permeability reflects the quantity of the free particle fraction in the interparticulate spaces of powder bed that leads to fine particle fraction during fluidization in air flow. A theoretical approach was developed in order to link the air permeability of powder bed and drag force acting on powders during aerosolization process. The permeability technique developed in this study provides a potential tool for screening Dry Powder Inhaler formulations at the development stage.
干粉吸入器近年来引起了制药科学家的极大关注，特别是那些由与较大载体颗粒结合并称为相互作用混合物的低剂量微粉化药物颗粒组成的干粉吸入器。然而，对于散装粉末性质（如粉末结构与其空气动力学分散性能之间的关系）的了解甚少。这项工作的目的是开发一种简单的方法来测量干粉吸入器中使用的相互作用混合物的空气透过率，使用勃氏仪——一种药典渗透性仪，并将其与空气动力学行为相关联。研究以丙酸氟替卡松和硫酸特布他林为药物模型，与几种乳糖混合，这些乳糖具有不同的粒径分布，因此含有不同比例的细颗粒乳糖。通过分析药物含量均匀度来检查混合物的质量。使用双级撞击器对细颗粒分数进行空气动力学评估。观察到对于测试的药物，散装特性 - 填充粉末床的空气透过率 - 与药物的细颗粒分数之间存在线性相关性。空气透过率反映了粉末床中颗粒间空间中自由颗粒分数的数量，在空气流中流化时会导致细颗粒分数。为了将粉末床的空气透过率与气溶胶化过程中粉末上的阻力联系起来，开发了一种理论方法。本研究中开发的渗透性技术为干粉吸入器制剂在开发阶段的筛选提供了一种潜在的工具。
