Formulation Technology Research Laboratories, Pharmaceutical Technology Division, Daiichi Sankyo Co., Ltd., 1-12-1, Shinomiya, Hiratsuka, Kanagawa 254-0014, Japan; Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Int J Pharm. 2017 Oct 30;532(1):118-123. doi: 10.1016/j.ijpharm.2017.08.085. Epub 2017 Aug 24.
As powder agglomeration during storage causes a decrease in the performance of dry powder inhalers (DPIs), it is important to understand the properties of powder agglomeration in developing DPIs. Generally, powder agglomeration is caused by capillary force and crystalline transformation in conditions of higher humidity. It is, however, difficult to correlate crystalline transformation and powder agglomeration, especially when the crystalline transformation is limited. In this study, we focused on the application of inverse gas chromatography (iGC) to detect powder agglomeration directly. There was a slight change between the powder state and lactose agglomerates using powder X-ray diffraction, and dynamic vapor sorption. On the other hand, a change in pressure drop was found during measurement of lactose using iGC. After measurement by iGC, powdered lactose agglomerated. This finding suggests that a pressure drop is related to powder agglomeration and can be employed to detect the onset of powder agglomeration. Based on these findings, we propose a novel index-the Void Forming Index (VFI)-which is related to the pressure drop with iGC. The VFI is a useful index in the evaluation of powder agglomeration, and will be especially useful during DPI development.
由于储存过程中的粉末团聚会降低干粉吸入剂（DPI）的性能，因此了解 DPI 开发过程中粉末团聚的特性非常重要。通常，在较高湿度条件下，由于毛细管力和晶体转变会引起粉末团聚。然而，很难将晶体转变和粉末团聚联系起来，特别是当晶体转变受到限制时。在这项研究中，我们专注于应用反气相色谱（iGC）来直接检测粉末团聚。使用粉末 X 射线衍射和动态蒸汽吸附，在粉末状态和乳糖团聚体之间只有细微的变化。另一方面，在使用 iGC 测量乳糖时，发现压降发生了变化。iGC 测量后，乳糖粉末团聚。这一发现表明压降与粉末团聚有关，可以用来检测粉末团聚的开始。基于这些发现，我们提出了一个新的指标——空隙形成指数（VFI）——它与 iGC 中的压降有关。VFI 是评估粉末团聚的有用指标，在 DPI 开发过程中尤其有用。
