Characterizing continuous powder mixing using residence time distribution

A review of the Residence Time Distribution (RTD) applications in solid unit operations

Effect of operating conditions and design parameters in a continuous powder mixer

An integrated approach for dynamic flowsheet modeling and sensitivity analysis of a continuous tablet manufacturing process

Continuous processing in pharmaceutical manufacturing is a relatively new approach that has generated significant attention. While it has been used for decades in other industries, showing significant advantages, the pharmaceutical industry has been slow in its adoption of continuous processing, primarily due to regulatory uncertainty. This paper aims to help address these concerns by introducing methods for batch definition, raw material traceability, and sensor frequency determination. All of the methods are based on established engineering and mathematical principles, especially the residence time distribution (RTD). This paper introduces a risk-based approach to address content uniformity challenges of continuous manufacturing. All of the detailed methods are discussed using a direct compaction manufacturing line as the main example, but the techniques can easily be applied to other continuous manufacturing methods such as wet and dry granulation, hot melt extrusion, capsule filling, etc.

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Using Residence Time Distributions (RTDs) to Address the Traceability of Raw Materials in Continuous Pharmaceutical Manufacturing

Processes involving particles, are known to exhibit extremely unpredictable behaviour, mainly due to the mesoscopic nature of granular media. Understanding particulate processes, not only for intellectual satisfaction, but also for process design and operation, basically requires a systems approach in modelling. Because they combine simplicity and flexibility, the stochastic models based on the Markov chain theory are very valuable mathematical tools to this respect. However, they are still largely ignored by the whole core of chemical engineering researchers. This motivates the existence of this review paper, in which we examine the three traditional issues: mixing and transport, separation and transformation.

Applications of Markov Chains in Particulate Process Engineering: A Review

Application of the theory of Markov chains to model different processes in particle technology

This paper is concerned with the investigation of the mixing process in a pilot scale continuous powder mixer, from both experimental and modelling points of view. A Markov chain model is proposed to simulate the residence time distribution (RTD) obtained from tracer experiments and detection by image analysis. The general model consists of 10 continuous stirred tank reactors with identical exchange coefficients and may serve as a basis for other applications. A 2D chain model is also developed and applied to take into account more features of real flow, such as crosswise mixing. Agreement between the model results and experimental data is more than reasonable, and gives a clear physical meaning to the parameters introduced. The characteristics of the process are controlled by the rotational speed of the mixer, which appears to be the key scale-up variable along with stirrer design.

Flow analysis and markov chain modelling to quantify the agitation effect in a continuous powder mixer

Experimental study of the stirring conditions taking place in a pilot plant continuous mixer of particulate solids

Continuous powder mixers offer a viable alternative to batch processes, but have received very little attention in scientific literature and in the industrial world. Mixer design is still very empirical and is not based on assessed methodologies. In this paper, we report experiments that aimed to compare two very different types of stirrers for a pilot-scale continuous powder mixer, and for two types of mixtures: a model mixture and a real pharmaceutical mixture. The first stirrer A is of the frame type with inclined paddles and internal transporting screw, the other stirrer B is of the shaft type with paddles mounted on it. Results are first presented from the viewpoint of bulk powder flow by hold-up determination and correlation with operating conditions. General relationships are derived which show that the mobile B leads to higher hold-ups, which may be an important drawback. The study of mixture homogeneity globally confirms these findings, especially in a dense phase flow regime. In the fluidised regime, where the stirrer B can be used, attention is drawn to the negative effect of excessive rotational speeds on the quality of the mixtures.

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Mizonov Vadim E

Papers

Applications of Markov Chains in Particulate Process Engineering: A Review

Application of the theory of Markov chains to model different processes in particle technology

Flow analysis and markov chain modelling to quantify the agitation effect in a continuous powder mixer

Experimental study of the stirring conditions taking place in a pilot plant continuous mixer of particulate solids

Influence of stirrer type on mixture homogeneity in continuous powder mixing: A model case and a pharmaceutical case