Adopting GMP standards
'By using a tumbler, different powders can be blended in a completely contained manner, with no environmental contamination, no need to load or unload powder into or out of a stand-alone mixer and no need to clean an additional piece of equipment,' said Vittoriano Marcheschi, managing director of Zanchetta, based in Lucca in Italy.
The use of dedicated bins for each product guarantees the identity of the batch and safe and fast operation throughout the entire process path, and practically all the industry's major players have integrated the concept into new and existing plants.
Zanchetta was one of the pioneers in this field, introducing its first Canguro tumbler in 1984. Marcheschi said: 'This machine was probably the first designed specifically for pharmaceutical applications, with concepts such as GMP design and finishing, stainless steel frame, single arm design and double inclination of the cradle to optimise mixing and ensure even distribution of actives included from its launch. The design has been adopted by several suppliers of mixing and handling equipment.'
He said that the future will be one of continuous improvement: adopting better GMP solutions, reducing the overall dimensions of the machines, adopting 'throughwall' concepts and integrating the machines into fully automatic plants. However, he did believe that continuous mixing is a technology which may have potential in the pharmaceutical industry, but only for large-scale production. This is a well-known technology in the food industry, but is difficult to implement in the pharmaceutical sector, where the importance of batch identity and the relatively small batch sizes have rendered it impractical thus far.
Other difficulties encountered occur when mixing small quantities of active ingredients with large quantities of excipients, especially when the physical characteristics of the raw materials are very different. 'It is always difficult to guarantee the homogeneity of the mixture when one component is present in quantities lower than 1-2%,' he said. 'In these cases it is possible to use tumblers with double inclinations, containers with internal buffers or with a special shape or to adopt multiple mixing steps. But at the end, when the product is really difficult and these solutions are not enough, the only way is to use wet granulation, incorporating the active by spraying a solution or dispersion during the liquid phase.'