Evaluation of particle size distribution of salmeterol administered via metered-dose inhaler with and without valved holding chambers

Background Administration of inhaled medications to very young children is sometimes difficult. Administration of inhaled medications via metered dose inhalers (MDIs) to pediatric patients younger than 4 years of age requires use of a holding chamber/spacer with an attached facemask. Objective This in vitro study was conducted to determine the particle size distribution and overall dose of salmeterol delivered in conjunction with the use of various US-marketed valved holding chambers (VHCs) in comparison to the dose-delivered via MDI without VHCs. Methods Cascade impaction methodology with high-performance liquid chromatography was used to evaluate the fine particle mass (FPM) of salmeterol administered without and with the use of the following VHCs: Optichamber, medium and large Aerochambers, adult Aerochamber, and medium Aerochamber Plus. Results Particle size distributions for the Optichamber, various sizes of Aerochamber, and the Aerochamber Plus were very similar and the particle size distributions for all VHCs were similar to the distribution of the control. The FPM for particles ranging from 0.7 to <3.3 μm in diameter (in the range shown to provide the greatest lung dose to negotiate the small airways of infants) was similar across the various VHCs tested. Statistical comparison of the fine particle fraction for these stages shows a very similar profile when differences from the salmeterol MDI control were evaluated. Conclusions In vitro results obtained under these test conditions demonstrate that all FPM values for the VHCs tested were within 15% of the control range, a difference that is unlikely to be clinically meaningful. These results indicate that the difference in FPM does not warrant a change in the recommended dosage of salmeterol administered when using the VHCs tested. Our results demonstrate that the use of an MDI and VHC provides a reasonable therapeutic approach for administration of salmeterol MDI to young children and other patients who have difficulties administering the MDI alone.

背景 给幼儿使用吸入性药物有时很困难。给4岁以下的儿科患者使用定量吸入器（MDI）给予吸入性药物时，需要使用带有连接面罩的储雾罐/ spacer。 目的 本项体外研究旨在确定与不使用储雾罐的MDI给药剂量相比，使用各种在美国销售的带阀储雾罐（VHC）时沙美特罗的粒径分布和总给药剂量。 方法 采用高效液相色谱级联撞击法评估在不使用以及使用以下储雾罐时沙美特罗的细颗粒质量（FPM）：Optichamber、中号和大号Aerochamber、成人Aerochamber以及中号Aerochamber Plus。 结果 Optichamber、各种尺寸的Aerochamber以及Aerochamber Plus的粒径分布非常相似，所有储雾罐的粒径分布与对照组的分布相似。直径在0.7至<3.3μm范围内（该范围显示能为婴儿的小气道提供最大肺部剂量）的颗粒的FPM在测试的各种储雾罐中相似。对这些阶段的细颗粒分数进行统计比较，当评估与沙美特罗MDI对照组的差异时，显示出非常相似的情况。 结论 在这些测试条件下获得的体外结果表明，测试的所有储雾罐的FPM值都在对照组范围的15%以内，这种差异不太可能具有临床意义。这些结果表明，FPM的差异并不意味着在使用测试的储雾罐时需要改变沙美特罗的推荐剂量。我们的结果表明，使用MDI和储雾罐为给幼儿和其他单独使用MDI有困难的患者使用沙美特罗MDI提供了一种合理的治疗方法。