Generally applicable breakage functions derived from single particle comminution data

Meier, M.; John, Edgar; Wieckhusen, Dierk; Wirth, W.

doi:10.1016/j.powtec.2009.03.018

Cited by 26 publications

(6 citation statements)

References 13 publications

(31 reference statements)

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“…This ratio was first suggested by Lawn and Marshall [ 133 ] to be indicative of a material's brittleness. In a follow-up study, Meier et al [ 134 ] studied the impact breakage of nine different materials by impacting their particles on rigid targets at different velocities and found that the breakage function is both size and material dependent. In a study by Gahn and Mersmann [ 128 ], an attrition model was proposed, which seems to be sufficiently accurate for the modeling of attrition in crystallizers [ 129 ].…”

Section: Processing: Impact Of Process Parameters Bead Material-smentioning

confidence: 99%

Nanomilling of Drugs for Bioavailability Enhancement: A Holistic Formulation-Process Perspective

et al. 2016

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Preparation of drug nanoparticles via wet media milling (nanomilling) is a very versatile drug delivery platform and is suitable for oral, injectable, inhalable, and buccal applications. Wet media milling followed by various drying processes has become a well-established and proven formulation approach especially for bioavailability enhancement of poorly water-soluble drugs. It has several advantages such as organic solvent-free processing, tunable and relatively high drug loading, and applicability to a multitude of poorly water-soluble drugs. Although the physical stability of the wet-milled suspensions (nanosuspensions) has attracted a lot of attention, fundamental understanding of the process has been lacking until recently. The objective of this review paper is to present fundamental insights from available published literature while summarizing the recent advances and highlighting the gap areas that have not received adequate attention. First, stabilization by conventionally used polymers/surfactants and novel stabilizers is reviewed. Then, a fundamental understanding of the process parameters, with a focus on wet stirred media milling, is revealed based on microhydrodynamic models. This review is expected to bring a holistic formulation-process perspective to the nanomilling process and pave the way for robust process development scale-up. Finally, challenges are indicated with a view to shedding light on future opportunities.

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Section: Processing: Impact Of Process Parameters Bead Material-smentioning

confidence: 99%

Nanomilling of Drugs for Bioavailability Enhancement: A Holistic Formulation-Process Perspective

et al. 2016

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“…Mat and W * m,min in (Equation 14) [73]. Interestingly, both parameters can be modeled as a function of fracture toughness K C and hardness H, i.e., in dependence of the intrinsic material parameters (see Figure 13b).…”

Section: Stirred Media Millingmentioning

confidence: 99%

“…The breakage function can be described by the superposition of at least two lognormal distributions. The mean sizes, the standard deviations of the two sub-distributions, and the coupling parameter between them all depend on the parameters

and

in (Equation (14)) [ 73 ]. Interestingly, both parameters can be modeled as a function of fracture toughness K C and hardness H, i.e., in dependence of the intrinsic material parameters (see Figure 13 b).…”

Section: Process Chain For Particle Formation and Formulationmentioning

confidence: 99%

Modeling and Simulation of Process Technology for Nanoparticulate Drug Formulations—A Particle Technology Perspective

Uhlemann

Diedam

Hoheisel³

et al. 2020

Pharmaceutics

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Crystalline organic nanoparticles and their amorphous equivalents (ONP) have the potential to become a next-generation formulation technology for dissolution-rate limited biopharmaceutical classification system (BCS) class IIa molecules if the following requisites are met: (i) a quantitative understanding of the bioavailability enhancement benefit versus established formulation technologies and a reliable track record of successful case studies are available; (ii) efficient experimentation workflows with a minimum amount of active ingredient and a high degree of digitalization via, e.g., automation and computer-based experimentation planning are implemented; (iii) the scalability of the nanoparticle-based oral delivery formulation technology from the lab to manufacturing is ensured. Modeling and simulation approaches informed by the pharmaceutical material science paradigm can help to meet these requisites, especially if the entire value chain from formulation to oral delivery is covered. Any comprehensive digitalization of drug formulation requires combining pharmaceutical materials science with the adequate formulation and process technologies on the one hand and quantitative pharmacokinetics and drug administration dynamics in the human body on the other hand. Models for the technical realization of the drug production and the distribution of the pharmaceutical compound in the human body are coupled via the central objective, namely bioavailability. The underlying challenges can only be addressed by hierarchical approaches for property and process design. The tools for multiscale modeling of the here-considered particle processes (e.g., by coupled computational fluid dynamics, population balance models, Noyes–Whitney dissolution kinetics) and physiologically based absorption modeling are available. Significant advances are being made in enhancing the bioavailability of hydrophobic compounds by applying innovative solutions. As examples, the predictive modeling of anti-solvent precipitation is presented, and options for the model development of comminution processes are discussed.

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“…There are three types of data obtainable from single-particle breakage: (i) functional relationship between stressing energy and corresponding product size distribution (Napier-Munn et al 1996;Petukhov and Kalman 2003;Vogel and Peukert 2005;Meier et al 2009;Rozenblat et al 2012), (ii) probability of particle breakage as a function of stressing energy (Krogh 1980;Austin 2002;Cho and Austin 2003;Peukert 2003Antonyuk et al 2005; Aman, Tomas, and Kalman 2010) and (iii) specific fracture energy or fracture strength distribution of a given material (Bourgeois 1993;Tavares and King 1998).…”

Section: Single-particle Breakage Testsmentioning

confidence: 99%

Influence of high-pressure grinding rolls on physical properties and impact breakage behavior of coarsely sized cement clinker

Camalan

Önal

2015

Particulate Science and Technology

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High pressure grinding rolls (HPGR) are widely used in cement clinker grinding prior to ball milling. The efficiency of HPGR was previously related to two capabilities: (a) efficient stressing mechanism, (b) weakening of particles which lead to finer product sizes after subsequent ball milling. This study aimed to investigate the influence of HPGR on the impact breakage behaviour of coarsely-sized cement clinker. Drop weight tests were conducted on three single-size samples from both feed and product streams of an industrial HPGR, so as to obtain impact breakage parameters: breakage probability and impact breakage functions. Radiographic, Vickers microhardness, BET, SEM, XRD, XRF and image processing methods were utilized to explain the variations in impact breakage parameters. The product samples were found to have less porosity than feed samples but they contained HPGR-induced micro-cracks. Those cracks are believed to be responsible for lower hardness and higher breakage probability of product particles than of feed ones under impact. However, fragments generated from the product samples by drop weight tests were coarser than those generated from feed samples. That was due to elimination of pores by HPGR action. At excess energy levels, both samples were broken to same extent regardless of structural differences.

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Generally applicable breakage functions derived from single particle comminution data

Cited by 26 publications

References 13 publications

Nanomilling of Drugs for Bioavailability Enhancement: A Holistic Formulation-Process Perspective

Nanomilling of Drugs for Bioavailability Enhancement: A Holistic Formulation-Process Perspective

Modeling and Simulation of Process Technology for Nanoparticulate Drug Formulations—A Particle Technology Perspective

Influence of high-pressure grinding rolls on physical properties and impact breakage behavior of coarsely sized cement clinker

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