Lu Xiang-Yun, Chen Lan, Wu Chuan-Yu, Chan Hak-Kim, Freeman Tim
School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
Freeman Technology Ltd., Tewkesbury GL20 8DN, UK.
Materials (Basel). 2017 May 29;10(6):592. doi: 10.3390/ma10060592.
The flowability and dispersion behavior are two important physicochemical properties of pharmaceutical formulations for dry powder inhalers (DPIs). They are usually affected by the environmental conditions, such as temperature and relative humidity (RH). However, very few studies have been focused on the relationship between the two properties and their dependence on RH during storage. In this research, model pharmaceutical formulations were prepared using mixtures of coarse and fine lactose. The fractions of fines in the mixtures were 0%, 5%, 10%, and 20%, respectively. These blends were stored at four different RH levels, 0%, 30%, 58%, and 85%, for 48 h. The FT4 Powder Rheometer was used to evaluate the powder flowability, and the Malvern Spraytec laser diffraction system was employed to assess the powder dispersion performance. The results indicated that both the flow and dispersion properties of lactose blends deteriorate after being stored at 85% RH, but improved after being conditioned at 58% RH. The fine particle fractions (FPFs) of the blends with 5% and 10% fine fractions and the as-received coarse lactose decreased when they were conditioned at 30% RH. For the blend with 20% fine fraction, a high RH during storage (i.e., 85% RH) affected the dispersion property, but had a limited influence on its flowability, while, for the coarse lactose powder, the different RH conditions affected its flowability, but not the dispersion results. A strong correlation between the powder flowability and its dispersion performance was found.
流动性和分散行为是干粉吸入剂（DPI）药物制剂的两个重要物理化学性质。它们通常受环境条件影响，如温度和相对湿度（RH）。然而，很少有研究关注这两个性质之间的关系以及它们在储存期间对相对湿度的依赖性。在本研究中，使用粗乳糖和细乳糖的混合物制备了模型药物制剂。混合物中细粉的比例分别为0%、5%、10%和20%。这些混合物在四个不同的相对湿度水平（0%、30%、58%和85%）下储存48小时。使用FT4粉末流变仪评估粉末的流动性，并采用马尔文喷雾技术激光衍射系统评估粉末的分散性能。结果表明，乳糖混合物在85%相对湿度下储存后，其流动性和分散性能均变差，但在58%相对湿度下调节后有所改善。含5%和10%细粉比例的混合物以及原样粗乳糖在30%相对湿度下调节后，其细颗粒分数（FPF）降低。对于含20%细粉比例的混合物，储存期间的高相对湿度（即85%相对湿度）影响其分散性能，但对其流动性影响有限，而对于粗乳糖粉末，不同的相对湿度条件影响其流动性，但不影响分散结果。发现粉末流动性与其分散性能之间存在很强的相关性。
