(M1230-11-64) A New Insight into the Effect of the Process Conditions on the Permeability of Powders

Purpose: Permeability of powders is the capacity of a powder to transmit a fluid, usually air, through its bulk (Zhao et al., 2021). Permeability influences the efficiency of many processes, as will be detailed hereafter. Therefore, measuring the permeability of a powder is important to understand its behavior in the processes, to improve the process efficiency, and to have better control of the quality of the final product. During the die-filling step in tablet manufacturing processes, the air must go out of the die through the powder to allow larger powder densification in the die. As a result, the permeability determines the weight uniformity, the packing fraction, and the tensile strength of the tablet. All these tablet characteristics, in turn, determine the quality of the final tablet in terms of disintegration and dissolution behavior of the tablet (Van Snick et al., 2017). In the capsule filling, permeability also affects the filling weight in dosator nozzle machines (Faulhammer et al., 2014). In dry powder inhalers, permeability affects the effective dispersion and release of an inhalation mixture (Shalash et al., 2018). Permeability has been already investigated for powders subjected to normal consolidation stresses above 3 kPa. But, in applications like die filling, the powder experiences low consolidation stresses and reaches low packing conditions. In these cases, it is important to measure the permeability at low consolidation conditions to properly analyze the powder behavior in the same conditions as in the process. Moreover, during the process, the packing fraction can vary because of the movements induced to the powder by the process itself. Therefore, it is also needed to study the effect of variation of packing fraction on the permeability. In this work, a new method combining an automatized tapped density measurement and a permeability measurement is proposed (Lupo et al., 2024). A set of common pharmaceutical excipients, characterized by different particle shapes and sizes, have been tested with the measurement device. The effect of packing fraction on permeability and the link with the flowability are analyzed.

Methods: A new procedure for the measurement of the permeability as a function of the packing fraction at low consolidation conditions has been developed. It consists of applying taps to the powder to control the powder packing fraction and measuring the resulting permeability. The latter has been measured by using an automated tapped density tester (GranuPack (Granutools, Belgium)) equipped with a measurement cell. Different lactose grades, characterized by different particle shapes and sizes, have been tested with the GranuPack. They are four SuperTab^® powders (S21AN, ST24AN, ST11SD, ST30GR) and three Pharmatose^® powders (P150M, P200M, and P450M).

Results: Figure 1 shows that all the powders present a decrease in the permeability with packing fraction. The curves do not follow a master curve showing that the packing fraction is not the only parameter influencing the permeability. In addition, depending on the packing fraction value, the permeability can change significantly. Therefore, it is important to measure the permeability in the same packing conditions of the process to avoid wrong estimations and to properly compare different powders. Figure 2 shows that the permeability classification changes depending on the packing conditions. In particular, the final permeability (measured after 500 taps) can be used to predict the powder flowability: the lower the HR the larger the permeability. Figure 3 shows that the more cohesive the powder, the larger the decrease of the permeability with the densification (Figure 3a) but the slower this decrease Figure 3b) compared to more flowable powders. Because of the link of the HR with the permeability ratio (k₀/k₅₀₀) and the Rate of variation of permeability (RoV_k), these two latter parameters could be used to complement the classical flowability indexes.

Conclusion: A new procedure for the measurement of the permeability as a function of the packing fraction at low consolidation conditions has been proposed. The results have shown that the larger the packing fraction the lower the permeability and, for some powders, a small modification of the packing fraction can lead to large variations in the permeability. Therefore, it is important to measure the permeability in the same densification condition of the process to properly compare the powders and design the process to maximize the efficiency or improve the product quality. It has been found that the powder classification can change depending on the densification conditions. Because of the direct correlation between the permeability at 500 taps and the powder cohesiveness, the permeability after the densification (500 taps) could be used to predict the powder flowability. Two new metrics have been proposed to quantify the effect of densification on permeability: the permeability ratio and the rate of variation of permeability. The results have shown that when the powder cohesiveness increases, the permeability ratio increases, and the rate of variation of permeability decreases. Therefore, these two parameters could help in predicting powder flowability.

References: Faulhammer, E., Llusa, M., Radeke, C., Scheibelhofer, O., Lawrence, S., Biserni, S., Calzolari, V., & Khinast, J. G. (2014). The effects of material attributes on capsule fill weight and weight variability in dosator nozzle machines. International Journal of Pharmaceutics, 471(1–2), 332–338.
Lupo, M., Neveu, A., Gemine, T., Francqui, F., & Lumay, G. (2024). Measuring permeability and flowability of powders at various packing fractions. Particuology.
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.
Van Snick, B., Holman, J., Cunningham, C., Kumar, A., Vercruysse, J., De Beer, T., Remon, J. P., & Vervaet, C. (2017). Continuous direct compression as manufacturing platform for sustained release tablets. International Journal of Pharmaceutics, 519(1–2), 390–407.
Zhao, Y., Phalswal, P., Shetty, A., & Kingsly Ambrose, R. P. (2021). Effects of powder vibration and time consolidation on soft and hard wheat flour properties. KONA Powder and Particle Journal, 38, 226–234.


Figure 1 Evolution of permeability k with the packing fraction for lactose powders. The error bars are reported only for the first and last measurement of each set and are based on three repetitions.


Figure 2 a) Initial permeability k0, b) final permeability k500, c) initial packing fraction, and d) final packing fraction as a function of the Hausner ratio HR for the set of lactose powders.


Figure 3 a) Permeability Ratio (k0/k500) and b) Rate of variation of permeability (RoVk) as a function of the HR for lactose powders