Ong Hui Xin, Traini Daniela, Loo Ching-Yee, Sarkissian Lala, Lauretani Gianluca, Scalia Santo, Young Paul M
Respiratory Technology, Woolcock Institute of Medical Research, The University of Sydney, NSW 2037, Sydney, Australia; Discipline of Pharmacology, Sydney Medical School, University of Sydney, NSW 2000, Australia.
Respiratory Technology, Woolcock Institute of Medical Research, The University of Sydney, NSW 2037, Sydney, Australia; Discipline of Pharmacology, Sydney Medical School, University of Sydney, NSW 2000, Australia.
Eur J Pharm Biopharm. 2015 Jun;93:320-7. doi: 10.1016/j.ejpb.2015.04.012. Epub 2015 Apr 27.
The study focuses on the application of a cell integrated modified Andersen Cascade Impactor (ACI) as an in vitro lung model for the evaluation of aerosols' behaviour of different formulation devices, containing the same active drug, specifically nebuliser, pressurised metered dose inhaler (pMDI) and dry powder inhaler (DPI). Deposition and transport profiles of the three different inhaled salbutamol sulphate (SS) formulations with clinically relevant doses were evaluated using a modified ACI coupled with the air interface Calu-3 bronchial cell model. Reproducible amounts of SS were deposited on Snapwells for the different formulations, with no significant difference in SS deposition found between the standard ACI plate and modified plate. The transport of SS aerosols produced from pMDI formulation had similar transport kinetics to nebulised SS but significantly higher compared to the DPI, which could have led to the differences in clinical outcomes. Furthermore, drug absorption of different inhaled formulation devices of the same aerodynamic fraction was found not to be equivalent due to their physical chemical properties upon aerosolisation. This study has established an in vitro platform for the evaluation of the different inhaled formulations in physiologically relevant pulmonary conditions.
该研究聚焦于一种细胞整合改良型安德森级联撞击器（ACI）作为体外肺模型的应用，用于评估含有相同活性药物（具体为雾化器、压力定量吸入器（pMDI）和干粉吸入器（DPI））的不同制剂装置中气溶胶的行为。使用改良型ACI与空气界面Calu-3支气管细胞模型相结合，评估了三种具有临床相关剂量的不同吸入用硫酸沙丁胺醇（SS）制剂的沉积和传输情况。不同制剂的SS在Snapwells上的沉积量可重现，标准ACI板和改良板之间的SS沉积无显著差异。pMDI制剂产生的SS气溶胶的传输动力学与雾化SS相似，但与DPI相比显著更高，这可能导致了临床结果的差异。此外，发现相同空气动力学粒径的不同吸入制剂装置的药物吸收并不等效，这是由于它们雾化后的物理化学性质所致。本研究建立了一个体外平台，用于在生理相关的肺部条件下评估不同的吸入制剂。
