R. Blanchard, R&D Manager, I Holland.
In January 2012, tablet tooling specialist I Holland and the University of Nottingham’s School of Pharmacy launched the two-year TSAR (Tabletting Science Anti-Stick Research) project to investigate and solve the most common tabletting issue of formulation ‘sticking’ to the tool face, which frequently results in long periods of downtime and substantial losses of product.
I talked to I Holland’s Rob Blanchard, R&D Manager, and Clare Taylor, Marketing Manager, about how TSAR will be used to help customers in the future to eliminate sticking and therefore protect productivity and profitability.
How many people are involved in the TSAR project and what are their roles?
Rob: There are six core people involved; four from I Holland and two from the University of Nottingham. From I Holland, there’s Chris Prideaux, the Managing Director, who is chairing the project, myself, the project lead, and Tim Sefton, an R&D engineer. All three of us have our own defined roles within the project, with Chris and I using Tim as a resource for carrying out compression trials and helping with the analysis of formulations and mechanical testing.
We also draw on other resources as and when needed, for example, the manufacturing team was instrumental in producing the samples that we’ve used for the project. Then there’s Dr. Abdennour Bouhroum, who is the associate from the University employed by I Holland as part of the project team. He is completing the analytical research for us. He’s planning and project managing the resources that are available to us at the University.
Also from the University, there’s Professor Clive Roberts, the academic lead, and Professor Morgan Alexander. They both have their own different skill sets and areas of expertise that are complimentary to the project.
Professor Roberts is Chair of the Pharmaceutical Nano Technology group and Director of the Nottingham Nano Technology Science Centre, both part of the Faculty of Science at the University. Clive has a fantastic reputation in the field of particle adhesion; he’s carried out many different studies looking into different kinds of adhesion. We’ve been working with Clive since 2009, so it’s not a new relationship.
Professor Alexander is Professor of Biomedical Services and Head of the Division of Biophysics at the Surface Analysis group, one area of his expertise and focus is on understanding surface interactions.
What are the factors that cause sticking and how is it currently dealt with?
Rob: TSAR is not the start of our anti-stick research as we began using advanced techniques such as atomic force microscopy to understand all the factors for sticking back in 2009.
There are several factors that we know have a major influence on sticking. I will start with the main ones. First to consider is Van der Waals forces or molecular attraction, which is when elements within the formulation are naturally attracted to elements within the tablet punch material. These forces are very low and can only be measured in nanonewtons but in bulk behaviour, when lots of these forces interact on the face of a tablet, they can cause sticking.
Another major influencer of sticking is capillary action, which can be linked to high moisture content. If moisture is present, there’s the potential for sticking in both direct compression or wet granulation. On the other hand, if the granules are very dry, you can get static electricity, also a major cause of sticking.
Those are the three main ones but there are others. You’ve also got the roughness or the morphology of the contact, or in other words, the punch tip face used to compress the powder. How that surface face interacts with the granule is critical.
Then you’ve got the deformation mechanics of the granule itself. Under compression, the granule is either elastic or plastic, which will have an influence again on sticking. So the characteristics of the granule itself under compression are also very important.
There’s also the environment that you are compressing in and that comes back to capillary action because if you have a very humid environment, then you’re going to get capillary action causing sticking.
Also linking back to Van der Waals forces, different chemistries on the punch tip face can influence sticking. For example, if Van der Waals forces are causing sticking where you’ve got chromium, the structure of the chemical coating can be changed so that the element is no longer present.
Understanding what factors cause sticking is what we did in 2009 to develop our PharmaCote range of coatings, way before TSAR started. The objective was that if we could understand what causes sticking, our R&D team could tailor the development of coatings for punch tip faces that prevent sticking. That’s what we’ve been doing since 2009 and as a result we’ve got a proven range of anti-stick solutions based on that research, but the one thing that could be improved across the industry is the ability of the tooling manufacturer to select the right coating solution straight away and that leads into what TSAR is really about.