Pharmaceutical Surface Science Research Group, Department of Pharmacy and Pharmacology, University of Bath, BA2 7AY Bath, UK.
DFE Pharma, Klever Strasse 187, 47574 Goch, Germany.
Int J Pharm. 2015 Jan 15;478(1):53-59. doi: 10.1016/j.ijpharm.2014.11.019. Epub 2014 Nov 13.
The aim of the study was to investigate how the fine particle content of lactose carriers prepared with different types of lactose fines regulates dry powder inhaler (DPI) formulation performance of a cohesive batch of micronised budesonide. Budesonide formulations (0.8 wt%) were prepared with three different lactose carriers (Lactohale (LH) LH100, 20 wt% LH210 in LH100 and 20 wt% LH300 in LH100). Fine particle fraction of emitted dose (FPFED) and mean mass aerodynamic diameter (MMAD) of budesonide was assessed with a Next Generation Impactor (NGI) using a Cyclohaler at 90 l/min. Morphological and chemical characteristics of particles deposited on Stage 2 were determined using a Malvern Morphologi G3-ID. The results indicate that increasing concentration of lactose fines (<4.5 μm) not only increased the FPFED but also the MMAD of budesonide, suggesting drug deposition in agglomerates. Presence of agglomerates on Stage 2 was confirmed by morphological analysis of particles. Raman analysis of material collected on Stage 2 indicated that the more fine lactose particles were available the more agglomerates of budesonide and lactose were delivered to Stage 2. These results suggest drug-fines agglomerate formation is an important mechanism for how lactose fines improve and regulate DPI formulation performance.
这项研究的目的是调查不同类型乳糖细粉制备的乳糖载体的细颗粒含量如何调节亲水性 budesonide 细粉的干粉吸入剂（DPI）制剂性能。使用三种不同的乳糖载体（Lactohale（LH）LH100、LH100 中 20wt%的 LH210 和 LH100 中 20wt%的 LH300）制备 budesonide 制剂（0.8wt%）。使用下一代撞击器（NGI）以 90l/min 的速度使用 Cyclohaler 评估 budesonide 的发射剂量的细颗粒分数（FPFED）和平均质量空气动力学直径（MMAD）。使用 Malvern Morphologi G3-ID 确定沉积在第 2 阶段的颗粒的形态和化学特性。结果表明，增加乳糖细粉（<4.5μm）的浓度不仅增加了 budesonide 的 FPFED，而且增加了 MMAD，表明药物在团聚体中沉积。通过对第 2 阶段颗粒的形态分析证实了团聚体的存在。对第 2 阶段收集的材料进行拉曼分析表明，更多可用的细乳糖颗粒导致更多的 budesonide 和乳糖团聚体被输送到第 2 阶段。这些结果表明，药物细粉团聚体的形成是乳糖细粉如何改善和调节 DPI 制剂性能的重要机制。
