(T1130-08-52) Effect of Packing Fraction on Permeability of Powders for Pharmaceutical Processes

Purpose: Powders are used in many pharmaceutical processes, such as tablet manufacturing, dry powder inhaler manufacturing, and capsule filling process. Therefore, it is important to precisely characterize the powders to properly control and optimize these processes. The factors affecting the macroscopic behavior of the powders in the processes are many: particle properties, e.g. size and shape distribution, cohesive forces, friction and interlocking between the particles, state of stress experienced by the powder in the process, and interaction with the surrounding fluid. Particularly, the influence of air is very important in pharmaceutical processes because it determines, for example, the quality of dispersion of the inhalation mixture in a dry powder inhaler (Shalash et al., 2018) or the efficiency of die-filling in the tablet manufacturing process (Vreeman & Sun, 2022). The property which quantifies the capacity of a material like a powder to transmit a fluid (e.g. air) through its bulk is called permeability. Permeability depends on the powder packing fraction: the larger the packing fraction, the lower the capacity of air to percolate through the material; on the opposite, the looser the powder, the bigger the space between the particles and the higher the permeability. Therefore, permeability strongly depends on the packing fraction. Because of the shear deformation induced on the powder by the pharmaceutical process where the powder is used, particles can rearrange to form a more or less compacted state, thus affecting the permeability and the efficiency of the process, where the powder is used. For example, an efficient tableting process requires a powder with an optimal permeability, that is sufficiently low to allow the powder to aerate and flow within the die and sufficiently high to fastly release the entrapped air and bring the particles closer, since the denser the powder in the die, the better the quality of the final tablet (Zakhvatayeva et al., 2018; Vreeman & Sun, 2022). Moreover, during the powder compression, the powder increases its packing fraction and consequently, its permeability reduces. Since the powder permeability depends on the packing fraction of the powder, it is necessary to measure the permeability at the same packing conditions reached by the powder in the process. Knowing the relationship between the variations in the packing fraction and the resulting evolution of permeability during the process is helpful for the proper formulation of the powders and the development of the process to improve the process efficiency.

Methods: A novel approach has been developed to study the correlation between the packing conditions and permeability of the powders. It consists in consolidating the powder bed through taps and evaluating the permeability of the powder bed at different packing conditions. An automated tapped density tester (GranuPack) has been used and equipped with a measurement cell to allow measuring the permeability. Seven different lactose powders, which are used in typical pharmaceutical processes and which differ in particle shape and size distribution, have been tested. Three of these are the Pharmatose^® ones (P150M, P200M, and P450M), and four of these are the SuperTab^® ones (ST21AN, ST24AN, ST11SD, ST30GR).

Results: Figure 1a shows the permeability of the lactose powders before applying any consolidation. Based on different permeability values, it is possible to classify the powders from the less permeable, i.e. the ST21AN, to the most permeable powder, i.e. the P450M. The differences in permeability values among all the powders derive from the different sizes and shapes of the particles, which affect the initial packing fraction. Because of taps, all the powders increase their packing fraction and the permeability decreases (Figure 1b) because of less space available for the air to permeate the powder bed. It is interesting to note, that, compared to the inial loose condition of the powder (Figure 1a), the classification in powder permeability changes after applying the taps (Figure 1b). In fact, after the consolidation, the most permeable powder is ST11SD while the less permeable one is P450M. This result is important because suggests that the permeability of the powders has to be measured in the same packing conditions as the process to have an accurate evaluation of powder permeability and to properly differentiate the powders, based on the permeability values

Conclusion: A new method has been proposed to study the effect of packing, induced by the taps, on the permeability, in packing conditions similar to those occurring in real pharmaceutical processes. The results show a direct link between the increase in the packing fraction and the decrease in permeability for the same powder. Moreover, the consolidation of powder can change the classification in powder permeability compared to that obtained in loose conditions. Therefore, it is important to measure the permeability in the same packing conditions occurring in the process for proper assessment of powder behavior in real pharmaceutical processes.

References: Shalash, A. O., Khalafallah, N. M., Molokhia, A. M., & Elsayed, M. M. A. (2018). The Relationship Between the Permeability and the Performance of Carrier-Based Dry Powder Inhalation Mixtures: New Insights and Practical Guidance. AAPS PharmSciTech, 19(2), 912–922.
Vreeman, G., & Sun, C. C. (2022). Air entrapment during tablet compression – Diagnosis, impact on tableting performance, and mitigation strategies. International Journal of Pharmaceutics, 615, 121514.
Zakhvatayeva, A., Zhong, W., Makroo, H.A., Hare, C., Wu, C.Y. (2018). An experimental study of die filling of pharmaceutical powders using a rotary die filling system. International Journal of Pharmaceutics, 553, 84-96.

Permeability of Pharmatose® powders (P150M, P200M and P450M) and SuperTab® powders (ST21AN, ST24AN, ST11SD and ST30GR): a) before (n=0) and b) after the application of 500 taps (n=500).