Technology Advancement and Commercialization, RTI International;
Technology Advancement and Commercialization, RTI International.
J Vis Exp. 2023 Aug 18(198). doi: 10.3791/65756.
Dry powder inhalers offer numerous advantages for delivering drugs to the lungs, including stable solid-state drug formulations, device portability, bolus metering and dosing, and a propellant-free dispersal mechanism. To develop pharmaceutical dry powder aerosol products, robust in vivo testing is essential. Typically, initial studies involve using a murine model for preliminary evaluation before conducting formal studies in larger animal species. However, a significant limitation in this approach is the lack of suitable device technology to accurately and reproducibly deliver dry powders to small animals, hindering such models' utility. To address these challenges, disposable syringe dosators were developed specifically for intrapulmonary delivery of dry powders in doses appropriate for mice. These dosators load and deliver a predetermined amount of powder obtained from a uniform bulk density powder bed. This discrete control is achieved by inserting a blunt needle to a fixed depth (tamping) into the powder bed, removing a fixed quantity each time. Notably, this dosing pattern has proven effective for a range of spray-dried powders. In experiments involving four different model spray-dried powders, the dosators demonstrated the ability to achieve doses within the range of 30 to 1100 µg. The achieved dose was influenced by factors such as the number of tamps, the size of the dosator needle, and the specific formulation used. One of the key benefits of these dosators is their ease of manufacturing, making them accessible and cost-effective for delivering dry powders to mice during initial proof-of-concept studies. The disposable nature of the dosators facilitates use in animal procedure rooms, where cleaning and refilling reusable systems and weighing materials is inconvenient. Thus, developing disposable syringe dosators has addressed a significant hurdle in murine dry powder delivery for proof-of-concept studies, enabling researchers to conduct more accurate and reproducible preliminary studies in small animal models for pulmonary drug delivery.
干粉吸入器为肺部给药提供了众多优势，包括稳定的固态药物制剂、设备便携性、定量给药和无推进剂的分散机制。为了开发药物干粉气溶胶产品，需要进行强大的体内测试。通常，初步研究涉及使用小鼠模型进行初步评估，然后在更大的动物物种中进行正式研究。然而，这种方法的一个显著限制是缺乏合适的设备技术，无法准确和可重复地将干粉输送给小动物，从而限制了这些模型的实用性。为了解决这些挑战，专门开发了一次性注射器定量器，用于以适合小鼠的剂量进行肺部干粉输送。这些定量器装载并输送来自均匀堆积密度粉末床的预定量的粉末。通过将钝针插入粉末床至固定深度（捣实）并每次去除固定量来实现这种离散控制。值得注意的是，这种给药模式已被证明对一系列喷雾干燥粉末有效。在涉及四种不同模型喷雾干燥粉末的实验中，定量器能够实现 30 至 1100 µg 范围内的剂量。实现的剂量受到许多因素的影响，例如捣实的次数、定量器针的大小以及使用的特定配方。这些定量器的一个关键优势是它们易于制造，这使得它们在进行初步概念验证研究时，能够以可负担得起的价格将干粉输送给小鼠。定量器的一次性性质便于在动物程序室中使用，在那里，清洁、重新填充可重复使用的系统和称重材料很不方便。因此，开发一次性注射器定量器解决了小鼠干粉输送中用于概念验证研究的一个重大障碍，使研究人员能够在小动物模型中进行更准确和可重复的初步研究，用于肺部药物输送。
