Die filling is a critical step during tableting as it affects the tablet’s critical quality attributes such as weight uniformity, porosity, and tensile strength, which lead to different disintegration and dissolution behaviors. This step is strongly influenced by the powder permeability, which can be defined as the capacity of a material to transmit a fluid, usually air, through its bulk. In fact, during the die-filling process, the air has to go out of the die to allow the entrance of the powder into the die. Also, the air entrained by the powder during die-filling has to escape from the powder to allow for a higher densification of the powder. The denser the powder in the die, the better are expected to be the tablet properties in terms of tensile strength, disintegration, and dissolution behavior [2].
In this work, lactose powders with different particle sizes and shapes (Pharmatose® 450M and SuperTab® 11SD, DFE Pharma, Germany), commonly used as excipients in pharmaceutical processes, have been investigated. In addition, mixtures of different SuperTab® grades (11SD, 30GR, and 21AN) and magnesium stearate (Peter Greven, Germany), used as a lubricant, have been prepared and tested. To measure the permeability at packing and consolidation conditions similar to the process, a new methodology has been developed, which combines the tapped density analysis with the GranuPack instrument (Granutools, Belgium) to control the powder densification through a defined number of taps, and the permeability at various packing fractions with a purposely developed permeability cell. The powders have been subjected to different numbers of taps, ranging from 0 to 500 taps, and the respective permeability has been measured to understand the effect of packing fraction on the permeability. Tablets composed of the aforementioned powders have been prepared with the STYLCAM 200R compaction simulator (Medelpharm, France). During tablet production, the filling height and the main compression force were maintained fixed, while six different paddle speeds (10, 20, 30, 40, 50, 60 %) and three tableting speeds (10, 25, 40 tab/min) were used. The permeability values, obtained at different packing fractions, have been compared with the properties of the tablets, obtained at different paddle and tableting speeds. In particular, we observe a correlation between the powder permeability and the tablet tensile strength, in accordance with recent literature [3]. The new insights gathered from this approach give a better understanding of the material properties and allow the development of improved formulations for better processability.
References
[1] C. Hildebrandt, S.R. Gopireddy, R. Scherließ, N.A. Urbanetz, Investigation of powder flow within a pharmaceutical tablet press force feeder – A DEM approach, Powder Technol. 345 (2019) 616–632.
[2] B. Van Snick, J. Holman, C. Cunningham, A. Kumar, J. Vercruysse, T. De Beer, J.P. Remon, C. Vervaet, Continuous direct compression as manufacturing platform for sustained release tablets, Int J Pharm. 519 (2017) 390–407.
[3] M.S. Escotet-Espinoza, S. Vadodaria, S. Ravendra, F.J. Muzzio, M.G. Ierapetritou, Modeling the effects of material properties on tablet compaction: A building block for controlling both batch and continuous pharmaceutical manufacturing processes, Int J Pharm 543 (2018) 274–287.