Purpose

To develop an in vitro method to rapidly evaluate regional lung doses delivered by pharmaceutical inhalers. Currently, cascade impactor measurements are used, but these are resource intensive and require significant post processing of in vitro data to arrive at regional deposition estimates.

Methods

We present a specialized filter apparatus that mimics tracheobronchial (TB) deposition of pharmaceutical aerosols emitted by commercially available dry powder inhalers (DPIs). The filter housing includes an electrostatic neutralizer to eliminate artificial electrostatic filtration effects. Regional deposition (tracheobronchial and alveolar) for four DPIs (Onbrez Breezhaler, Flovent Diskus, Pulmicort Turbuhaler, and Asmanex Twisthaler) was estimated using cascade impactor measurements and an in silico regional deposition model. These estimates were compared to direct measurements of regional deposition as provided by the TB filter mimic and an absolute filter placed downstream of the TB filter housing, representing the alveolar dose.

Results

The two methods were shown to provide similar estimates of extrathoracic, tracheobronchial, and alveolar deposition, as well as total recovery of active pharmaceutical ingredients.

Conclusions

Because of its design, the TB filter apparatus makes it possible to estimate regional deposition with inhalers directly using variable inhalation profiles without any additional equipment or changes to the experimental configuration. This method may be useful to expedite development of both innovative and generic drug products as it provides regional respiratory tract deposition estimates using fewer resources than exisiting methods.

中文翻译：

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使用过滤器估计干粉吸入器的局部肺沉积

目的

开发一种体外方法来快速评估药物吸入器提供的区域肺剂量。目前，使用级联撞击器测量，但这些测量是资源密集型的，并且需要对体外数据进行大量后处理才能得出区域沉积估计。

方法

我们提出了一种专门的过滤装置，可模拟由市售干粉吸入器 (DPI) 排放的药物气溶胶的气管支气管 (TB) 沉积。过滤器外壳包括一个静电中和器，以消除人工静电过滤效应。使用级联冲击器测量和计算机区域沉积模型估计了四种 DPI（Onbrez Breezhaler、Flovent Diskus、Pulmicort Turbuhaler 和 Asmanex Twisthaler）的区域沉积（气管支气管和肺泡）。将这些估计与 TB 过滤器模拟提供的区域沉积的直接测量值和放置在 TB 过滤器外壳下游的绝对过滤器进行比较，代表肺泡剂量。

结果

这两种方法显示出对胸外、气管支气管和肺泡沉积以及活性药物成分的总回收率的相似估计。

结论

由于其设计，TB 过滤装置可以直接使用可变吸入曲线估计吸入器的区域沉积，而无需任何额外的设备或更改实验配置。这种方法可能有助于加快创新和仿制药产品的开发，因为它使用比现有方法更少的资源提供区域呼吸道沉积估计。