Uniforme poedermengsels: mengen beschouwd als een deeltjesverkleiningsproces

OBJECTIVE To identify the basic mechanisms of agglomerate breakage during powder blending. Presence of drug agglomerates in a blend poses a potential safety risk in e.g. pharmaceutical applications. Therefore, agglomerates need to be removed. DESIGN AND METHODS This study assessed the critical process parameters and rules that must be observed when scaling up a mixing process. RESULTS Experiments using so-called brittle calibrated test particles provided evidence that agglomerates reduce in size via an abrasion mechanism. The abrasion rate is not only influenced by the (mechanical) properties of agglomerates and process conditions, but also by the particle size distribution of the filler. A novel method to measure powder velocities enabled the development of a quantitative model that describes the relationships between powder motion during blending and agglomerate abrasion. A Stokes number (Stabr) defined as the ratio between the kinetic energy density of the bed and the work of fracture of agglomerates predicts the rate of agglomerate abrasion very well. CONCLUSION Particle velocity critically affects agglomerate abrasion and mixing time. Therefore mixing of a powder blend containing a cohesive material should be approached as a particle size reduction problem rather than a distribution issu

Uniform powder mixtures: blending as a particle size reduction process

OBJECTIVETo identify the basic mechanisms of agglomerate breakage during powder blending. Presence of drug agglomerates in a blend poses a potential safety risk in e.g. pharmaceutical applications. Therefore, agglomerates need to be removed.DESIGN AND METHODSThis study assessed the critical process parameters and rules that must be observed when scaling up a mixing process. RESULTSExperiments using so-called brittle calibrated test particles provided evidence that agglomerates reduce in size via an abrasion mechanism. The abrasion rate is not only influenced by the (mechanical) properties of agglomerates and process conditions, but also by the particle size distribution of the filler. A novel method to measure powder velocities enabled the development of a quantitative model that describes the relationships between powder motion during blending and agglomerate abrasion. A Stokes number (Stabr) defined as the ratio between the kinetic energy density of the bed and the work of fracture of agglomerates predicts the rate of agglomerate abrasion very well.CONCLUSIONParticle velocity critically affects agglomerate abrasion and mixing time. Therefore mixing of a powder blend containing a cohesive material should be approached as a particle size reduction problem rather than a distribution issu

Blending of agglomerates into powders 1: Quantification of abrasion rate

A very common situation in the pharmaceutical arena is that a small amount of cohesive drug substance needs to be distributed in a large bulk of free-flowing filler such as lactose. The key topic of attention is that aggregates of a cohesive drug substance need to be sufficiently broken up in an acceptable time-frame. This implies that there is need for a better mechanistic understanding of the blending process and the reduction in size of the aggregates. The purpose of this study is to obtain more insight in the mechanisms that lead to the break up of assemblies of powder particles in a moving powder bed. The break up of aggregates was studied by application of so-called brittle Calibrated Test Particles (bCTPs). These are well-defined aggregates with brittle fracture properties. The dominant mechanism of the break up of these aggregates is abrasion by multiple impacts. There is evidence of a relationship between strength (expressed as porosity) of the bCTPs and rate of abrasion. This is often a slow process and the rate is determined riot only by the (mechanical) properties of the agglomerates and process conditions, but also by the particle size distribution of the bulk filler. (C) 2009 Elsevier B.V. All rights reserved

Kinetic energy density and agglomerate abrasion rate during blending of agglomerates into powders

Problems related to the blending of a cohesive powder with a free flowing bulk powder are frequently encountered in the pharmaceutical industry. The cohesive powder often forms lumps or agglomerates which are not dispersed during the mixing process and are therefore detrimental to blend uniformity. Achieving sufficient blend uniformity requires that the blending conditions are able to break up agglomerates, which is often an abrasion process. This study was based on the assumption that the abrasion rate of agglomerates determines the required blending time. It is shown that the kinetic energy density of the moving powder bed is a relevant parameter which correlates with the abrasion rate of agglomerates. However, aspects related to the strength of agglomerates should also be considered. For this reason the Stokes abrasion number (St(Abr)) has been defined. This tAbr, parameter describes the ratio between the kinetic energy density of the moving powder bed and the work of fracture of the agglomerate. The St(Abr) number is shown to predict the abrasion potential of agglomerates in the dry-mixing process. It appeared possible to include effects of filler particle size and impeller rotational rate into this concept. A clear relationship between abrasion rate of agglomerates and the value of St(Abr) was demonstrated. (C) 2011 Elsevier B.V. All rights reserved

A statistical method for velocity detection in moving powder beds using image analysis

An existing method to measure particle velocity is particle image velocimetry which requires presence of tracer materials. This method of contrast enhancement is not always applicable in an industrial setting. Therefore a method to assess the movement of small, structures has been introduced, called powder surface velocimetry (PSV). The principle of PSV is to follow the movement of small structures on the surface of the powder bed. The displacement of the structure is correlated with velocity. The rate of the blade of a blender was quantified to assess the validity of PSV. Next the powder surface velocity of lactose 100 M was measured by PSV and was found to be in line with expected values and flow regimes. (c) 2011 American Institute of Chemical Engineers AIChE J, 201

Quantitative Characterization of Agglomerate Abrasion in a Tumbling Blender by Using the Stokes Number Approach

<p>Removal of microcrystalline cellulose agglomerates in a dry-mixing system (lactose, 100 M) predominantly occurs via abrasion. The agglomerate abrasion rate potential is estimated by the Stokes abrasion (St(Abr)) number of the system. The St(Abr) number equals the ratio between the kinetic energy density of the moving powder bed and the work of fracture of the agglomerate. Basically, the St(Abr) number concept describes the blending condition of the dry-mixing system. The concept has been applied to investigate the relevance of process parameters on agglomerate abrasion in tumbling blenders. Here, process parameters such as blender rotational speed and relative fill volumes were investigated. In this study, the St(Abr) approach revealed a transition point between abrasion rate behaviors. Below this transition point, a blending condition exists where agglomerate abrasion is dominated by the kinetic energy density of the powder blend. Above this transition point, a blending condition exists where agglomerates show (undesirable) slow abrasion rates. In this situation, the blending condition is mainly determined by the high fill volume of the filler.</p>