Marco Lupo1, Michela Beretta2, Geoffroy Lumay3, Aurélien Neveu1, Filip Francqui1
1Granutools, Rue Jean-Lambert Defrêne, 107, 4340 Awans, Belgium
2Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010, Graz, Austria
3GRASP, University of Liège, Belgium.
Tablet manufacturing is an important process in the pharmaceutical industry as tablets are the most common oral solid dosage form. Producing a tablet can be challenging as the manufacturing process involves many steps, which must be controlled to guarantee that the final product satisfies the quality and safety standards. Those steps include: (i) the preparation of the powder mixture, composed of active pharmaceutical ingredient(s) and excipients, (ii) the die filling, where the powder enters into the die, (iii) the powder compaction, where the tablet is formed and (iv) the tablet ejection [1].
Die filling is a critical step during tableting as it affects tablet’s critical quality attributes such as weight uniformity, porosity and tensile strength, that 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].
Depending on the process conditions and the characteristics of the powder, like the shape and size of the particles, the powder can reach either higher or lower packing fractions, defined as the ratio between bulk and true density, with a consequently lower or higher permeability. Therefore, it is necessary to know exactly the packing conditions reached by the powder in the process to predict the die filling efficiency and the tablet characteristics. In addition, during the die filling step, the powder experiences low consolidation stress, being the powder typically filled into the die by the paddle with a horizontal movement. Therefore, it is necessary to estimate the powder permeability in similar consolidation conditions.
To measure the permeability at packing and consolidation conditions similar to the process, a new methodology has been developed, which combines the capacity of the GranuPack instrument (Granutools, Belgium) to control the powder densification through a defined number of taps, and the possibility of measuring the permeability at various packing fractions with a purposely developed permeability cell.
In this work, lactose powders with different 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. 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 produced tablets were investigated for their critical quality attributes. The permeability values, obtained at different packing fractions, have been compared with the properties of the tablets, obtained at different paddle and tableting speeds. 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. https://doi.org/10.1016/J.POWTEC.2019.01.040.
[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. https://doi.org/10.1016/j.ijpharm.2017.01.010.