Miyamoto Kahori, Taga Hiroaki, Akita Tomomi, Yamashita Chikamasa
Department of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Pharmaceutics. 2020 Oct 15;12(10):976. doi: 10.3390/pharmaceutics12100976.
Recently, statistical techniques such as design of experiments are being applied for efficient optimization of oral formulations. To use these statistical techniques for inhalation formulations, efficient methods for rapid determination of the aerodynamic particle size distribution of many samples are needed. Therefore, we aimed to develop a simple method to measure aerodynamic particle size distribution that closely agrees with the results of inhalation characteristic tests. We added attachments for dispersion to the aerodynamic particle sizer (APS) so that formulations could be dispersed under the same condition as for multi-stage liquid impinger (MSLI) measurement. Then, we examined the correlation between MSLI and APS using lyophilizate for dry powder inhalation formulations that generate porous particles just on inhalation. It is difficult to obtain the accurate aerodynamic particle size distribution of porous particles by APS because the particle density is difficult to estimate accurately. However, there was a significant correlation between MSLI and APS when the particle density settings for APS measurement was calculated by a conversion factor based on the result of MSLI. The APS with dispersion attachments and this conversion factor can measure a number of samples in a short time, thereby enabling more efficient optimization of dry powder inhalers.
最近，诸如实验设计等统计技术正被应用于口服制剂的高效优化。为了将这些统计技术用于吸入制剂，需要有能快速测定多个样品空气动力学粒径分布的有效方法。因此，我们旨在开发一种简单的方法来测量空气动力学粒径分布，使其与吸入特性测试结果高度吻合。我们在空气动力学粒度分析仪（APS）上添加了分散附件，以便制剂能在与多级液体冲击器（MSLI）测量相同的条件下分散。然后，我们使用用于干粉吸入制剂的冻干品来研究MSLI和APS之间的相关性，该冻干品在吸入时会产生多孔颗粒。通过APS很难获得多孔颗粒准确的空气动力学粒径分布，因为颗粒密度难以准确估计。然而，当基于MSLI的结果通过换算系数计算APS测量的颗粒密度设置时，MSLI和APS之间存在显著相关性。带有分散附件的APS和此换算系数可以在短时间内测量多个样品，从而实现干粉吸入器更高效的优化。
