(M1330-08-46) Impact of Material Attributes and Critical Process Parameters on Low Dose Powder Filling Using Drum Filler System

Purpose: Low dose powder filling forms an important component of dry powder inhaler (DPI) manufacturing. There are multiple methods that exist for low powder filling such as tamp filling, dosator filling, vacuum dosator filling and vacuum drum 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. In this study, we have evaluated a vacuum drum filling system by Harro Hofliger to understand the impact of material attributes (density, particle size distribution, and flowability) and process parameters (vacuum pressure, drum bore size, and stirrer type) on in-process controls (fill weight and %RSD) for capsule filling process.

Methods: Pharmaceutical powders with different material attributes were selected and filled in size 3 capsules using Harro Hofliger’s DrumLab (table 1). 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. Powders were filled at different vacuum pressures using drum 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 stirrer geometries (standard stirrer and asymmetric stirrer).

Results: Study demonstrated that 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. However, higher %RSD was observed with LH300 and formulation A. Additionally, asymmetric stirrer led to lower %RSD and higher dosing compared to standard stirrer for LH300 and formulation A which could be attributed to its paddle shaped geometry.

Conclusion: Drum filling is an efficient method for low-dose 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 the overall filling process.

Table 1: Material attributes of the selected powders



Table 2: Fill weight and %RSD for LH300 using 30mm3 bore size drum



Figure 1: Results - Lactohale 300 (Fill weight (mg) vs. No. of fills) using 30 mm3 and 7.5 mm3 Drum