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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.

While it would provide many advantages from many aspects, the application of continuous mixing processes to the pharmaceutical field is still in its infancy. In this paper we report results concerning the continuous mixing of nine ingredients (including three actives) that constitute a current drug. We examine these results in the light of different pharmaceutical process constraints, such as mixture quality control, time-stability of this quality, sensitivity of the process to perturbations. The apparatus is a pilot plant Gericke GCM 500 continuous mixer with three loss-in-weight feeders. A specific experimental protocol is developed to determine the homogeneity of the mixtures at the outlet of the mixer. The homogeneity of the mixtures is examined through industrial standards that would allow the product to be released on the market. The steady-state operation is first reported on, and it is demonstrated that a very acceptable mixture can be produced under certain conditions, with excellent time stability. The response of the mixer to filling sequences of two critical feeders is also quantified in terms of mixture homogeneity. It is found that it may be preferable to stop the process during these periods.

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The many methods which exist to characterise the quality of a powder mixture have been recently reviewed and linked with mixing mechanisms in current literature. In this paper, we try to develop a novel methodology for defining and characterising homogeneity using principal component analysis (PCA) as an alternative to well-known statistical methods, such as auto-correlation functions or variances. We apply this to image analysis for the case of a powder mixture flowing out of a continuous mixing device. An emphasis is placed on the calculation in real-time of the degree of homogeneity of loose materials on the conveyor belt, carrying this mixture. Mass flow disturbances applied to a binary mixture are studied by the proposed methodology, which is found to be sensitive to small structural defaults.

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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 holdup determination and correlation with operating conditions. General relationships are derived which show that the mobile B leads to higher holdups , 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.