Formulation Technology Research Laboratories, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan; Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Formulation Technology Research Laboratories, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
Int J Pharm. 2020 Oct 15;588:119766. doi: 10.1016/j.ijpharm.2020.119766. Epub 2020 Aug 13.
Dry powder inhaler (DPI) is an attractive alternative for non-invasive drug administration and can make the use of critical biopharmaceutical formulations more convenient for patients. Inhalation of biopharmaceutical formulations can provide targeted delivery to the lungs as well as systemic delivery. Generally, biopharmaceutical DPI formulations consist of highly cohesive powders that tend to agglomerate. For successful delivery to the lungs, the detection of powder cohesiveness and its effect on the performance of the formulations is mandatory. Herein, the effects of the physical properties of mannitol on the cohesiveness of DPI formulations were investigated. The powder cohesion was detected using the void forming index (VFI) measured by inverse gas chromatography (iGC) at 4 h (VFI), which was defined as the pressure drop ratio of 4 h purged sample to that of the initial sample. VFI was found to correlate well with the cohesiveness of DPI formulations. The amount of investigated samples required for VFI measurement was less than that required for conventional measurements. VFI showed a good relationship between the cohesiveness of DPI formulations and the physical properties of mannitol. Thus, VFI can be a reliable standard index to evaluate the cohesiveness of DPI formulations.
干粉吸入器（DPI）是一种有吸引力的非侵入性药物给药替代方法，可使患者更方便地使用关键的生物制药配方。吸入生物制药配方可以提供靶向肺部的输送以及全身输送。通常，生物制药 DPI 配方由具有高内聚性的粉末组成，这些粉末往往会团聚。为了成功输送到肺部，必须检测粉末的内聚性及其对配方性能的影响。本文研究了甘露醇的物理性质对 DPI 配方内聚性的影响。使用反向气相色谱（iGC）在 4 小时（VFI）测量的空隙形成指数（VFI）检测粉末内聚性，VFI 定义为 4 小时吹扫样品与初始样品的压力降比。发现 VFI 与 DPI 制剂的内聚性很好地相关。用于 VFI 测量的样品量少于常规测量所需的样品量。VFI 显示了 DPI 制剂的内聚性与甘露醇物理性质之间的良好关系。因此，VFI 可以成为评估 DPI 制剂内聚性的可靠标准指标。
