(267h) DEM Simulation of Bin Blending Considering Different Scales | AIChE

(267h) DEM Simulation of Bin Blending Considering Different Scales


Jajcevic, D., Research Center Pharmaceutical Engineering Gmbh
Khinast, J. G., Graz University of Technology
Turki, R., Pfizer UK Ltd
Wong, S. M., Pfizer UK Ltd
Sarkar, A., Worldwide Research and Development, Pfizer Inc.
Doshi, P., Worldwide Research and Development, Pfizer Inc.
Bin blending is a crucial step in the solid dosage form manufacturing in pharmaceutical industries. One of the main challenges in this process is reaching the desired content uniformity while avoiding over-blending. Over-blending may increase the powder cohesiveness, especially in cases where the amount of lubricant is low. This may disturb the subsequent processes i.e., tablet press or capsule filling and preferred to be avoided. Also, over-blending may lead to over-lubrication, reducing bioavailability.

Several studies were performed in this field with a main focus on content uniformity, whereas over-blending drew less attention. In this study, experiments and discrete element method (DEM) simulations are implemented to study the blending process with a focus on both content uniformity and over blending effect. According to our experiments, powder cohesiveness is increasing during the process. However, the trend of this increase is not the same at different scales. At the smallest scale (lab scale), one hour of blending leads to have a cohesive powder. In contrast, in the production scale, around 10 minutes blending brings about a cohesive product which challenges the blending time. In order to understand the reasons for this behaviour and to avoid them, 4 scales of a bin blenders (from 2.5 litre to 100 litre) considering various operational conditions are simulated in this work. The effect of rotational speed (rpm), loading mass percentage, and the powder cohesiveness is investigated by means of particles velocity, travelling distance, shear stress, and blending time. Due to the computational limits of simulating 2.5 kg to 45 kg of powder with real particle size distribution, particles are scaled considering DEM contact force model parameter calibration. A total 35 cases with the number of particles in the range of 4 to 60 million are modelled. For the post-processing, studied parameters, i.e., travelling distance, shear stress, and blending time are extrapolated by applying the relay race method. Moreover, particles velocity is calculated based on a rotating cylindrical coordinate system considering blender rotational axis as the cylinder axis.

Results can be divided into three main sections: 1. Detailed study of the influence of operational condition on the studied parameters. 2. The correlation between parameters crossing different scales. 3. The relation between the powder cohesiveness gained from experiments and studied parameters from DEM simulation. In the first section, it is observed that by increasing loading mass the velocity and travel distance is decreased. This causes longer blending time compare to less loading mass in the system. Moreover, particles are exposed to higher shear stress when the bin is loaded with more mass. Rotational speed investigation reveals that particles at the surface layers gain higher speed by increasing the RPM. In contrary, shear stress on particles is not affected by rotational speed. Moreover, results of the simulations with a more cohesive powder show dramatic increase in shear stress. Second section brings the geometry size effect on the studied parameters. According to the results, blending time is mostly influenced by the loading mass percentage in the system in different scales. However, the shear stress is higher in the larger blenders. Particle velocity and distance travel are also increased by the bin size. Finally, in the third section, powder flow function coefficients (FFC) gained from blended powder in various operational condition are correlated with the shear stress from the respective simulations. According to the results, powder FFC decreases with the particles exposed to shear. In other words, conditions, such as higher loading and longer blending time, are making powder more cohesive. The cut-off time of the acceptable FFC value can be selected from the trend and compared to blending time. If content uniformity is not satisfied through this time, the loading mass inside the bin should be reduced to reach the content uniformity as well as avoid cohesive product.