Evolution in revolution

'I don't think there have been any major technical advances over the last several years,' says Dr Tom Chirkot, lab manager at US company Patterson Kelley, based in East Stroudsburg, Pennsylvania. 'Essentially, the same machines that have been used for many years are still being used today. The advances have been in increasing the adaptability and utility of the mixing devices.

'For example, at PK we offer extended blades on the intensifier bar to increase the range of material volume that can be processed well in a certain size mixer. Previously we were constrained to a range of about +/-10% in working volume but with extended blades we can under-load to 60 or 70% of the proper working volume and still do a good job of high speed and liquid/solids mixing,' Chirkot commented.

Another innovation is PK's new M.V.P blending system. This allows a single mixing station to become adaptable to many different sized vessels and also to tumble or high speed mixing. A Smart Blender control system provides user-friendly access, batch records, recipe control and other state-of-the-art features. 'The increasing sophistication of logic controllers is another innovation. The controllers can feed back copious amounts of information about the process, allowing an operator to maintain tighter control and also enabling the operator to be in a remote location, safe from high potency drugs,' Chirkot said.

He pointed out that provided the proper machine is chosen for the operation then the mixing step will work well. 'The major problems occur when the formulation leaves the mixing vessel and this usually involves segregation. Some have tried to overcome segregation by inducing mass flow conditions. They have done this with special inserts in the vessel or tried to modify vessel design to a particular discharge angle that will aid mass flow.'

Segregation during transport throughout the plant has been addressed by making the transport vessel into a mixing vessel so that a re-mixing can occur, usually at the tablet press area. PK's M.V.P. is an example of this type of thinking. 'In my opinion, the way to deal with segregation is to introduce a wet granulation step that will firmly entrench the batch in a state of homogeneity.'

Beyond segregation, Chirkot thought the biggest challenges that lie ahead include real time detection of homogeneity, more rigorous scale-up rules and more precise analysis of mixing action. 'There are several potential methods for real time detection of mix homogeneity. Our efforts with the TC probe that measures effusivity is one method with tremendous potential.'

Defining the movement within a mixing vessel is certainly a very complex problem to solve, he pointed out, but some people are looking at chaos theory and others at fractal analysis to model movement in mixers. Another area related to defining mixing motion is greater specificity of the mixer to individual formulations. 'Pharmaceutical formulators are aware that each formulation has individual qualities distinct from others. This means that optimum mixing speed and movement for formulation A is different than formulation B,' Chirkot stressed.