(198n) Scale-up Study for Low Dose Powder Filling Using Vacuum Drum Filling Syste­m

Dry powder inhaler (DPI) manufacturing involves handling of low dose formulations. There are multiple methods exist for low dose DPI filling but powder filling in milligram fill weight is still a challenge. As most of the pharmaceutical powders are poor flowing and show unpredictable flow behavior, this filling process becomes even more difficult when process is transferred from lab to pilot scale. In this study, we have evaluated lab scale (DrumLab) and pilot scale (ModuC LS) vacuum drum filling system by Harro Hofliger to understand the impact of scale up on overall filling performance.

Methods:

For this study, powders with different properties were selected and filled in size 3 HPMC capsules using ModuC LS and DrumLab. The selected materials were Lactohale 300/LH300 (poor flow with D50 5µm), Inhalac 230 (fair flow with D50 90µm) and in-house formulation A (very poor flow). The selected powders were filled using both the equipment at different vacuum levels, using different types of stirrers and drum sizes. At the end, the capsule fill weight and %RSD was recorded. The data obtained from DrumLab was compared with the ModuC LS results to understand the scalability.

Results:

The fill weights obtained using ModuC LS were higher than fill weights achieved using DrumLab. For example, with LH300, using ModuC LS and standard stirrer at 200 mbar, 400 mbar and 600 mbar vacuum levels the fill weight was 12.23mg, 14.24mg, and 15.17mg respectively. With DrumLab and standard stirrer at 200 mbar, 400 mbar and 600 mbar vacuum levels the fill weight obtained was 11.031mg, 13.531mg, and 14.486mg respectively. Additionally, we observed higher %RSD with DrumLab in comparison to ModuC LS. The variation in fill weights and %RSD could be attributed to the difference in hopper geometries, powder feeding mechanism and stirrer size.

Conclusions:

The scale up study for vacuum drum filling was conducted using lab scale DrumLab and pilot scale ModuC LS for powders with different properties. Vacuum drum filing system is an efficient method for low dose powder filling and can be easily scaled from laboratory to pilot scale.