Seifelnasr Amr, Si Xiuhua, Xi Jinxiang
Department of Biomedical Engineering, University of Massachusetts, Lowell, MA 01854, USA.
Department of Aerospace, Industrial and Mechanical Engineering, California Baptist University, Riverside, CA 92504, USA.
Pharmaceutics. 2024 May 19;16(5):683. doi: 10.3390/pharmaceutics16050683.
The standard multi-dose nasal spray pump features an integrated actuator and nozzle, which inevitably causes a retraction of the nozzle tip during application. The retraction stroke is around 5.5 mm and drastically reduces the nozzle's insertion depth, which further affects the initial nasal spray deposition and subsequent translocation, potentially increasing drug wastes and dosimetry variability. To address this issue, we designed a new spray pump that separated the nozzle from the actuator and connected them with a flexible tube, thereby eliminating nozzle retraction during application. The objective of this study is to test the new device's performance in comparison to the conventional nasal pump in terms of spray generation, plume development, and dosimetry distribution. For both devices, the spray droplet size distribution was measured using a laser diffraction particle analyzer. Plume development was recorded with a high-definition camera. Nasal dosimetry was characterized in two transparent nasal cavity casts (normal and decongested) under two breathing conditions (breath-holding and constant inhalation). The nasal formulation was a 0.25% w/v methyl cellulose aqueous solution with a fluorescent dye. For each test case, the temporospatial spray translocation in the nasal cavity was recorded, and the final delivered doses were quantified in five nasal regions. The results indicate minor differences in droplet size distribution between the two devices. The nasal plume from the new device presents a narrower plume angle. The head orientation, the depth at which the nozzle is inserted into the nostril, and the administration angle play crucial roles in determining the initial deposition of nasal sprays as well as the subsequent translocation of the liquid film/droplets. Quantitative measurements of deposition distributions in the nasal models were augmented with visualization recordings to evaluate the delivery enhancements introduced by the new device. With an extension tube, the modified device produced a lower spray output and delivered lower doses in the front, middle, and back turbinate than the conventional nasal pump. However, sprays from the new device were observed to penetrate deeper into the nasal passages, predominantly through the middle-upper meatus. This resulted in consistently enhanced dosing in the middle-upper turbinate regions while at the cost of higher drug loss to the pharynx.
标准的多剂量鼻喷雾泵具有集成的促动器和喷嘴,这在使用过程中不可避免地会导致喷嘴尖端缩回。缩回行程约为5.5毫米,会大幅减少喷嘴的插入深度,进而影响初始鼻喷雾沉积和后续的药物转移,可能会增加药物浪费和剂量测定的变异性。为了解决这个问题,我们设计了一种新的喷雾泵,将喷嘴与促动器分离,并用一根柔性管连接它们,从而消除了使用过程中的喷嘴缩回。本研究的目的是在喷雾生成、羽流发展和剂量测定分布方面,将新装置的性能与传统鼻泵进行比较测试。对于这两种装置,使用激光衍射颗粒分析仪测量喷雾液滴尺寸分布。用高清摄像机记录羽流发展情况。在两种呼吸条件(屏气和持续吸气)下,在两个透明鼻腔模型(正常和充血)中对鼻腔剂量测定进行表征。鼻腔制剂是含有荧光染料的0.25% w/v甲基纤维素水溶液。对于每个测试案例,记录鼻腔内喷雾的时空转移情况,并在五个鼻腔区域对最终递送剂量进行量化。结果表明,两种装置在液滴尺寸分布上存在微小差异。新装置产生的鼻羽流具有更窄的羽流角度。头部方向、喷嘴插入鼻孔的深度以及给药角度在决定鼻喷雾的初始沉积以及随后液膜/液滴的转移方面起着关键作用。通过可视化记录增强了鼻腔模型中沉积分布的定量测量,以评估新装置带来的递送增强效果。使用延长管时,改进后的装置产生的喷雾输出较低,并且与传统鼻泵相比,在前、中、后鼻甲处递送的剂量较低。然而,观察到新装置的喷雾能更深入地穿透鼻道,主要通过中鼻道上部。这导致中鼻甲上部区域的给药量持续增加,但代价是咽部的药物损失更高。