(602b) Powder Fluidization in Dry Powder Inhalers

Lactose powders are utilized in Dry Powder Inhalers (DPI) as carriers for Active Pharmaceutical Ingredient (API) particles to improve their fluidization [1]. Carrier-carrier and carrier-wall collisions result in the release of API particles from the carrier particles, and they determine the fine particle fraction (FPF) of API leaving the DPI which is of crucial importance in treatment outcomes [2]. The dynamics of carrier particles is affected by their physical properties, fluid turbulence and device geometry [3]. Powder fluidization has been studied in the literature probing these effects in commercial DPIs both experimentally and computationally by Coates et al. [4, 5]. Turbulent channel flows of carrier particles with different properties have been studied experimentally by Mahmoudi et al. [6], measuring the powder evacuation time at various Reynolds numbers.

We study, by means of Computational Fluid Dynamics - Discrete Element Method (CFD-DEM) simulations, the fluidization of carrier particles in turbulent channel flows, comparing the particles evacuation times obtained numerically with the experimental results of Mahmoudi et al. [6]. After this validation study, we examine the effect of device geometry on carrier particle evacuation dynamics. Subsequently, we perform DPI simulations with a representative dose containing both carrier and API particles to probe the effect of device geometry on FPF.

[1] Newman, S. P., Chan, H. K. In vitro/in vivo comparisons in pulmonary drug delivery. J Aerosol Med Pulm Drug Deliv. 2008; 21(1): 77.

[2] A. Kourmatzis, S. Cheng, H.K. Chan, Airway geometry, airway flow, and particle measurement methods: implications on pulmonary drug delivery, Expert Opinion Drug Deliv. 15 (2018) 271–282.

[3] J.S. Shrimpton, M. Danby, Effect of poly-dispersity on the stability of agglomerates subjected to simple fluid strain fields, Powder Technol. 228 (2012) 241–249.

[4] M.S. Coates, H.K. Chan, D.F. Fletcher, et al., Influence of air flow on the performance of a dry powder inhaler using computational and experimental analyses, Pharm. Res. 22 (2005) 1445–1453.

[5] M.S. Coates, H.K. Chan, D.F. Fletcher, et al., Effect of design on the performance of a dry powder inhaler using computational fluid dynamics. Part 2: Air inlet size, J. Pharm. Sci. 95 (2006) 1382–1392.

[6] Mahmoudi, S., Elserfy, K., Cheng, S., Chan, H. K., Hebbink, G., & Kourmatzis, A. (2019). Fluidisation characteristics of lactose powders in simple turbulent channel flows. Experimental Thermal and Fluid Science, 103, 201-213