(420d) An Innovative Approach to Studying Sifting Segregation: DEM Enabled Scale Down

Segregation is an unwanted phenomenon that can occur when handling powder mixture. It poses challenges to uniformity in product quality and, therefore, needs to be understood and mitigated [1].

During the discharge of powders from a hopper, a specific form of segregation can occur, commonly referred to as the sifting mechanism. A widely used experimental test to study sifting segregation is summarized in Shah et al.’s study [2]. In this approach, the powder mixture is discharged from one hopper to another multiple times. This transfer of material between hoppers forces the mixture to segregate if there is high segregation potential, enabling the gauging of the segregation tendency of the mixture under study. In short, the segregation tester consists of three hoppers: hopper A-1, A-2, and hopper B. Hoppers A-1 and A-2 have the same design and are low-angled, with hopper A-2 equipped with sample collectors. Hopper B is a steep-angled hopper. Initially, the powder mixture is discharged from hopper B to hopper A-1, followed by three additional transfers in the order of A1 to A2, A2 to A-1, and A-1 to A2. At the end of the segregation test, samples are collected for analysis [2].

In the pharmaceutical industry, conducting sifting segregation experiments as outlined in Shah et al.’s study [2] using the hopper size specified in that study can present significant challenges, both in terms of cost and time constraints. Access to the necessary amount of active pharmaceutical ingredient (API) for each experiment is often limited, especially during the early stages of development when the required quantities may not be available. Additionally, to reduce the uncertainty of the experiments, the test needs to be repeated at least three times, further increasing the prohibitive nature of using this segregation tester in some cases. Advanced simulation techniques, such as the Discrete Element Method (DEM), can potentially be utilized to gain insights into sifting segregation [3]. Similarly, performing full-scale DEM simulations of the sifting segregation tester can be computationally demanding, even when utilizing proposed acceleration techniques such as coarse-graining or pseudo-2-D simulation. These obstacles demonstrate the necessity for a novel and efficient approach when examining sifting segregation occurring during hopper discharge.

In this study, we present a novel approach to address these challenges by adopting a scale-down methodology inspired by the concept commonly employed when studying mixing tanks/bio-reactors. Our proposed approach involves designing scaled-down hoppers using DEM while maintaining flow regimes and stress levels experienced by the powder consistent between the actual and scaled-down hoppers. In our proposed approach, the DEM simulation of the full-scale hopper needs to be performed once to identify the flow regime and stress levels experienced by particles at the original scale. Variations of small-scale hoppers are then simulated to obtain the equivalent small-scale design of the full-scale. Once the small-scale hopper design is identified, the sifting segregation experiments can be carried out in considerably less time and utilizing fewer physical resources compared to using the original size hoppers for studying sifting segregation.

[1]. Jakubowska, Emilia, and Natalia Ciepluch. "Blend segregation in tablets manufacturing and its effect on drug content uniformity—a review." Pharmaceutics 13.11 (2021): 1909.

[2]. Shah, Keyur R., et al. "Assessment of segregation potential of powder blends." Pharmaceutical development and technology 12.5 (2007): 457-462.

[3] Hadi, Ahmed, et al. "DEM Modelling of Segregation in Granular Materials: A Review." KONA Powder and Particle Journal 41 (2024): 78-107.