Chiesi Farmaceutici S.p.A., Parma, Italy.
Wolfson School of Mechanical and Manufacturing Engineering, Loughborough University, Loughborough, United Kingdom.
Int J Pharm. 2015 Dec 30;496(2):780-91. doi: 10.1016/j.ijpharm.2015.10.072. Epub 2015 Nov 3.
Effective drug delivery to the lungs by a DPI device requires the air-stream through the device to have sufficient power to aerosolise the powder. Furthermore, sufficient turbulence must be induced, along with particle-wall and particle-particle collisions, in order to de-aggregate small drug particles from large carrier particles. As a result, the emitted and the fine particle doses produced by many commercially available DPI devices tend to be strongly affected by the natural inter-patient variability of the inhaled air flow. The Nexthaler® is a multi-dose breath-actuated dry-powder inhaler with minimum drug delivery-flow rate dependency and incorporating a dose protector. The actuation mechanism of the dose-protector ensures that the dose is only exposed to the inhaled air flow if the flow has sufficient power to cause complete aerosolisation. For this study, a proprietary lactose placebo powder blend was filled into "transparent" Nexthaler® to allow application of high-speed imaging and particle image velocimetry (PIV) techniques to successfully interrogate and reveal details of the powder entrainment and emission processes coupled with characterisation of the flow environment in the vicinity of the mouthpiece exit. The study showed that fluidisation of the bulk of the powder occurs very quickly (∼20ms) after withdrawal of the dose protector followed by powder emission from the device within ∼50ms thereafter. The bulk of the metered placebo dose was emitted within 100-200ms. The visualisation study also revealed that a very small fraction of powder fines is emitted whilst the dose protector still covers the dosing cup as the flow rate through the device accelerates. The PIV results show that the flow exiting the device is highly turbulent with a rotating flow structure, which forces the particles to follow internal paths having a high probability of wall impacts, suggesting that the flow environment inside the Nexthaler® DPI will be very beneficial for carrier-drug de-aggregation.
干粉吸入器通过空气流将药物有效递送至肺部，这要求设备中的空气流具有足够的动力来使粉末气溶胶化。此外，为了从小载体药物颗粒上解聚出小药物颗粒，必须同时诱导足够的湍流以及颗粒-壁和颗粒-颗粒碰撞。因此，许多市售的干粉吸入器产生的发射剂量和细颗粒剂量往往会受到吸入气流的个体间自然差异的强烈影响。Nexthaler®是一种多剂量、呼吸驱动的干粉吸入器，对药物输送气流速率的依赖性最小，并包含剂量保护器。剂量保护器的致动机制确保只有在吸入气流具有足以引起完全气溶胶化的足够动力时，才会使剂量暴露于吸入气流中。在这项研究中，将专有的乳糖安慰剂粉末混合物填充到“透明”Nexthaler®中，以便应用高速成像和粒子图像测速（PIV）技术来成功询问和揭示粉末夹带和发射过程的细节，并结合口件出口附近的流动环境进行特征描述。研究表明，在剂量保护器缩回后，大部分粉末迅速流化（约 20ms），随后装置内的粉末在大约 50ms 后喷出。大部分计量的安慰剂剂量在 100-200ms 内被发射。可视化研究还揭示了在粉末通过装置时流速加速，剂量保护器仍覆盖剂量杯的一小部分粉末细粉被发射。PIV 结果表明，从装置中排出的气流具有很强的湍流，具有旋转的流动结构，这迫使颗粒遵循具有高壁碰撞概率的内部路径，这表明 Nexthaler®干粉吸入器内部的流动环境将非常有利于载体药物解聚。
