(536p) Optimization of Low Dose Powder Filling Process for Dry Powder Inhalers

Dry powder inhaler (DPI) manufacturing involves handling low dose formulations. There are multiple methods exist for low dose DPI filling such as tamp filling, dosator filling, vacuum dosator filling and vacuum drum filling but powder filling in milligram fill weight is still a huge challenge.

As most of the pharmaceutical powders are poor flowing and show unpredictable flow behavior, this filling process becomes even more difficult and challenging. In this study, we have evaluated lab scale and pilot scale vacuum drum filling system by Harro Hofliger to understand the critical material attributes (powder density, particle size distribution and flowability) and critical process parameters (vacuum fill pressure, drum bore size, and stirrer type) on fill weight and %RSD for the DPI capsule filling process. The overall goal of this study was to optimize the vacuum drum filling process.

Methods:

During this study, pharmaceutical powders with different material properties were selected (table 1) and filled in size 3 capsules using Harro Hofliger’s DrumLab (lab scale) and ModuC LS (pilot scale). Among the selected powders Lactohale 300/LH300, Inhalac 230 and Inhalac 120 are poor, fair and good flowing powders respectively. We have also evaluated an in-house formulation A. unlike other selected materials, proprietary formulation A was highly cohesive and low-density (<100g/l) demonstrating very poor flow properties. The selected powders materials were filled at different vacuum pressure levels using drum of bore size 7.5mm³ and 30mm³, and net fill weight of each capsule was recorded to study fill weight variation (%RSD) and product density (mg/mm³). Additionally, the impact of stirrer geometry on fill weight and %RSD was also studied using two types of stirrers including standard stirrer and asymmetric stirrer. The standard stirrer is commonly used to fill good to fair flowing powders whereas asymmetric stirrer is suitable for poor flowing and cohesive powders.

Results:

The fill weight was a function of vacuum pressure and linear relationship was observed between fill weight and vacuum pressure (table 2) for all materials except Inhalac 120 as it is a good flowing powder. However, higher %RSD was observed with LH300 and formulation A at lower fill levels especially with standard stirrer. The asymmetric stirrer led to lower %RSD and higher fill weight compared to standard stirrer for LH300 (figure 1) and formulation A which could be attributed to its paddle shaped geometry.

Conclusions:

Vacuum drum filling is an efficient method for low dose powder filling and can be easily scaled from laboratory to pilot scale. However, it is important to understand the material attributes to determine process parameters such as vacuum pressure, drum bore size and type of stirrer to optimize overall filling process.

Keywords:

Low-dose filling, Drum filler, DrumLab