No abstract

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.

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.