Modeling of milling processes via DEM, PBM, and microhydrodynamics

Bilgili, Ecevit; Capece, Maxx; Afolabi, Afolawemi

doi:10.1016/b978-0-08-100154-7.00007-7

Cited by 12 publications

(11 citation statements)

References 116 publications

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“…In contrast, relatively scant information is available about the processing/operational challenges, such as energy-intensive operation, high cost due to high energy consumption, long operating hours, and contamination of drug particles by the beads [ 22 , 25 , 26 ]. Overcoming these challenges entails a mechanistic understanding of the impact of process variables—such as the stirrer speed, the size/material of the beads, and the bead loading—on the breakage kinetics, milling time required for a desired product fineness, energy consumption, and media wear [ 27 , 28 ]. Here, we focus on the breakage kinetics, as they relate to production cycle time: faster breakage results in shorter processing to achieve a desired nanoparticle size.…”

Section: Introductionmentioning

confidence: 99%

Kinetic and Microhydrodynamic Modeling of Fenofibrate Nanosuspension Production in a Wet Stirred Media Mill

2021

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This study examined the impact of stirrer speed and bead material loading on fenofibrate particle breakage during wet stirred media milling (WSMM) via three kinetic models and a microhydrodynamic model. Evolution of median particle size was tracked via laser diffraction during WSMM operating at 3000–4000 rpm with 35–50% (v/v) concentration of polystyrene or zirconia beads. Additional experiments were performed at the center points of the above conditions, as well as outside the range of these conditions, in order to test the predictive capability of the models. First-order, nth-order, and warped-time kinetic models were fitted to the data. Main effects plots helped to visualize the influence of the milling variables on the breakage kinetics and microhydrodynamic parameters. A subset selection algorithm was used along with a multiple linear regression model (MLRM) to delineate how the breakage rate constant k was affected by the microhydrodynamic parameters. As a comparison, a purely empirical correlation for k was also developed in terms of the process/bead parameters. The nth-order model was found to be the best model to describe the temporal evolution; nearly second-order kinetics (n ≅ 2) was observed. When the process was operated at a higher stirrer speed and/or higher loading with zirconia beads as opposed to polystyrene beads, the breakage occurred faster. A statistically significant (p-value ≤ 0.01) MLRM of three microhydrodynamic parameters explained the variation in the breakage rate constant best (R2 ≥ 0.99). Not only do the models and the nth-order kinetic–microhydrodynamic correlation enable deeper process understanding toward developing a WSMM process with reduced cycle time, but they also provide good predictive capability, while outperforming the purely empirical correlation.

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Section: Introductionmentioning

confidence: 99%

Kinetic and Microhydrodynamic Modeling of Fenofibrate Nanosuspension Production in a Wet Stirred Media Mill

2021

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“…Moreover, some integral properties play a significant role in numerous real-world applications of the PBE including fluidized bed granulators [5], pharmaceutical studies [7,10] etc. Mathematically, these properties are generally described by the moments of the number density distribution in the following form:…”

Section: Introductionmentioning

confidence: 99%

“…Linear fragmentation results from external forces or internal stresses acting on the particles, while nonlinear fragmentation is additionally driven by collisions or interactions among particles, as illustrated in figure 1. Nonlinear fragmentation mechanisms play a crucial role in various physical and engineering processes, such as the bulk distribution of raindrops [1,2], communication systems [3,4], fluidized beds [5], and various types of crushing and milling processes [6,7]. One specific form of the nonlinear process is the pure binary collisional fragmentation , where we assume that collisions between two particles are inelastic and instantaneous, resulting in the fragmentation of either one or both of the colliding particles.…”

Section: Introductionmentioning

confidence: 99%

Homotopy perturbation method and its convergence analysis for nonlinear collisional fragmentation equations

Yadav,

Das,

Singh

et al. 2023

Proc. R. Soc. A.

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The exploration of collisional fragmentation pheno-mena remains largely unexplored, yet it holds considerable importance in numerous engineering and physical processes. Given the nonlinear nature of the governing equation, only a limited number of analytical solutions for the number density function corresponding to empirical kernels are available in the literature. This article introduces a semi-analytical approach using the homotopy perturbation method to obtain series solutions for the nonlinear collisional fragmentation equation. The method presented here can be readily adapted to solve both linear and nonlinear integral equations, eliminating the need for domain discretization. To gain deeper insights intothe accuracy of the proposed method, a convergence analysis is conducted. This analysis employs the concept of contractive mapping within the Banach space, a well-established technique universally acknowledged for ensuring convergence. Various collisional kernels (product and polymerization kernels), breakage distribution functions (binary and multiple breakage) and various initial particle distributions are considered to obtain the new series solutions. The obtained results are successfully compared against finite volume method [26] solutions in terms of number density functions and their moments. The error between the exact and obtained series solutions is shown in plots and tables to confirm the applicability and accuracy of the proposed method.

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“…However, there is limited information available for solving the processingoperational challenges such as cost due to high energy consumption, long operating hours, and contamination of drug particles by the beads [8,11]. Solving these problems entails a mechanistic understanding of the impact of process parameters such as the stirrer speed, the size and material of the beads, the bead loading, the suspension flow rate, and the drug loading on the breakage kinetics, specific energy consumption, media wear, and milling time required for the desired product fineness [12,13].…”

Section: Introductionmentioning

confidence: 99%

A Novel Intensification Strategy for Wet Media Milling of Drug Suspensions: Bead Mixtures

Guner

Kannan

Berrios

et al. 2020

Proceedings of the 1st International Electronic Conference on Pharmaceutics

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Nano-sized drug particle formation is one of the most popular approaches in dissolution enhancement of poorly water-soluble drugs. However, it requires process optimization since it is a time consuming and costly method. The aim of this study is to investigate the impact of various mixtures of crosslinked polystyrene (CPS) and yttrium-stabilized zirconia (YSZ) beads (YSZ:CPS = 0:100-100:0 %v:%v) on the breakage kinetics and energy consumption during the wet stirred media milling (WSMM) of fenofibrate (FNB, BCS II drug). Five WSMM experiments were conducted using 3000 rpm stirrer speed and 50% volumetric bead loading with a suspension of 10% FNB, 7.5% HPC-L, and 0.05% SDS. Laser diffraction was used for the determination of particle sizes. Breakage rate, power required by the mill, and specific energy consumption were analyzed for all mixture runs. The experimental data show that YSZ beads provided faster breakage than the CPS beads, as signified by the lower time constant of the former. On the other hand, CPS beads required lower stirrer power than the YSZ beads. When both cycle time and specific energy consumption were considered for process optimality, YSZ-CPS bead mixtures performed better than YSZ or CPS alone and the optimal bead mixture was found.

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Modeling of milling processes via DEM, PBM, and microhydrodynamics

Cited by 12 publications

References 116 publications

Kinetic and Microhydrodynamic Modeling of Fenofibrate Nanosuspension Production in a Wet Stirred Media Mill

Kinetic and Microhydrodynamic Modeling of Fenofibrate Nanosuspension Production in a Wet Stirred Media Mill

Homotopy perturbation method and its convergence analysis for nonlinear collisional fragmentation equations

A Novel Intensification Strategy for Wet Media Milling of Drug Suspensions: Bead Mixtures

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