Heida Rick, Hagedoorn Paul, van Meel Melle C, Prins Jurrie E R, Simonis Frederike S, Akkerman Renate, Huckriede Anke L W, Frijlink Henderik W, de Boer Anne H, Hinrichs Wouter L J
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, 9713 AV Groningen, The Netherlands.
Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands.
Pharmaceutics. 2023 Jun 28;15(7):1847. doi: 10.3390/pharmaceutics15071847.
A challenge in the development of dry powder formulations for inhalation is the poor reproducibility of their administration to small laboratory animals. The currently used devices for the pulmonary administration of dry powder formulations to small rodents often function sub-optimally as they use the same puff of air for both powder dispersion and aerosol delivery. As a result, either the air volume and flow rate are too low for complete powder deagglomeration or they are too high for effective aerosol delivery to the lungs of the animal. Therefore, novel and better devices are desired. We here present an aerosol generator designed to administer a pre-generated aerosol to the lungs of mice. By mapping the complex relationship between the airflow rate, delivery time and emitted dose, we were able to control the amount of powder being delivered from the aerosol generator. The emitted aerosol had a size range favorable for lung deposition and could be measured reproducibly. Nevertheless, in vivo fluorescent imaging still revealed considerable differences between the mice in terms of the dose deposited and the distribution of powder over the lungs, suggesting that a certain biological variation in lung deposition is inevitable.
开发用于吸入的干粉制剂面临的一个挑战是,将其给予小型实验动物时重现性较差。目前用于向小型啮齿动物肺部给药干粉制剂的装置通常功能欠佳,因为它们使用同一股气流来进行粉末分散和气溶胶递送。结果,要么空气体积和流速过低,无法使粉末完全解聚,要么过高,无法将有效气溶胶递送至动物肺部。因此,需要新颖且更好的装置。我们在此展示一种气溶胶发生器,其设计用于将预先生成的气溶胶递送至小鼠肺部。通过绘制气流速率、递送时间与发射剂量之间的复杂关系,我们能够控制从气溶胶发生器递送的粉末量。发射的气溶胶具有有利于肺部沉积的粒径范围,并且可以重现性地测量。然而,体内荧光成像仍显示,小鼠在沉积剂量和肺部粉末分布方面存在相当大的差异,这表明肺部沉积存在一定的生物学差异是不可避免的。