Benque Benedict, Khinast Johannes G
Institute for Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13, 8010 Graz, Austria.
Institute for Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13, 8010 Graz, Austria; Research Center for Pharmaceutical Engineering, Inffeldgasse 13, 8010 Graz, Austria.
Eur J Pharm Sci. 2021 Jan 1;156:105574. doi: 10.1016/j.ejps.2020.105574. Epub 2020 Sep 25.
Drug delivery from a capsule-based dry powder inhaler depends on the inhaler's design, the drug's formulation, and the inhalation maneuver. The latter affects both the air flow and the capsule motion in the inhaler. It is well known that patient-to-patient variability is a major challenge in the design of new inhaler types. Modeling and simulation are important tools for understanding such systems, yet quite complex. Simulation studies of capsule-based dry powder inhalers have disregarded the transient nature of the inhalation process, adopting a constant flow rate through the inhaler instead. In addition, either no capsules, a capsule in a fixed position, or a capsule rotating at a constant rate have been considered. In this work, literature data for three inhalation flow profiles were incorporated into coupled simulations of the air flow and carrier particle motion through an Aerolizer® dry powder inhaler with a rotating capsule and compared to simulations at constant air flow rates. The results for the profile simulations indicated that the carrier powder experienced larger velocity fluctuations. Acceleration events were tracked as a measure of collision- and flow-induced dispersion. The majority of fast particle accelerations occurred when the particles collided with the swirl chamber walls. Of the two common particle dispersion metrics, only the peak particle force distribution appeared to be sensitive to the inhalation profiles, while the effect of the profiles on the cumulative impulse was small.
基于胶囊的干粉吸入器的药物递送取决于吸入器的设计、药物的配方以及吸入动作。后者会影响吸入器中的气流和胶囊运动。众所周知，患者之间的变异性是新型吸入器设计中的一个主要挑战。建模和模拟是理解此类系统的重要工具，但相当复杂。基于胶囊的干粉吸入器的模拟研究忽略了吸入过程的瞬态特性，而是采用通过吸入器的恒定流速。此外，要么不考虑胶囊，要么考虑固定位置的胶囊，要么考虑以恒定速率旋转的胶囊。在这项工作中，将三种吸入气流曲线的文献数据纳入了通过带有旋转胶囊的Aerolizer®干粉吸入器的气流和载体颗粒运动的耦合模拟中，并与恒定气流速率下的模拟进行了比较。曲线模拟的结果表明，载体粉末经历了更大的速度波动。跟踪加速事件作为碰撞和流动引起的分散的一种度量。大多数快速颗粒加速发生在颗粒与涡流室壁碰撞时。在两种常见的颗粒分散度量中，只有峰值颗粒力分布似乎对吸入曲线敏感，而曲线对累积冲量的影响较小。
