TSAR Predict service solves age-old 'sticking' conundrum in hours

It is a year since I first spoke to I Holland Ltd’s research, development & quality systems manager Rob Blanchard about I Holland and the University of Nottingham’s School of Pharmacy’s TSAR (Tabletting Science and Anti-Stick Research) project, the sole aim of which has been to solve the most prevalent tabletting issue of formulation ‘sticking’ to the punch tip face. As forecast, TSAR Predict — the resulting and much-hyped solution that aims to put an end to sticking by straightaway providing a right-first-time answer as to the ideal PharmaCote tooling coating for any formulation — is finally here. I recently spoke to Rob again to learn how TSAR Predict works and what it means for I Holland customers now and in the future.

On 6 February 2014 — two years since I Holland and the University of Nottingham’s School of Pharmacy embarked on this mammoth project, headed up by Rob and chair of pharmaceutical nanotechnology at the University of Nottingham professor Clive Roberts — TSAR Predict was launched by way of a webinar entitled ‘Solving Your Sticking Problems with Tabletting Science’, available on the I Holland website (http://bit.ly/1k6Cf6i). Hosted by Rob and Professor Roberts, the webinar culminated in an explanation of how two years’ research findings had been incorporated into the mathematical model TSAR Predict, helping to speed up the process of selecting the most suitable of I Holland’s PharmaCote anti-stick punch coatings for any sticky formulation.

So how does TSAR Predict actually work? It is really very simple, with I Holland requiring only the name of the API and or excipients to make a prediction. The key parameters are then entered into TSAR Predict to obtain the predicted particle adhesion force against each of the nine PharmaCote anti-stick coatings in I Holland’s range. “This gives a strong indication as to whether the formulation will adhere to our anti-stick solutions,” affirmed Rob. “The mathematical model is a combination of different formulas — based on a multitude of Van der Waals, capillary and electrostatic calculations obtained during the project — which directly correlate with each of our PharmaCote coatings, providing the predicted particle adhesion force that will be experienced with each.” Obviously, the lower the force, the more suitable that coating is going to be.

In instances where the product is in development and ingredient information is classified — as is often the case in the pharmaceutical industry — I Holland is still able to use to use the model to suggest a suitable solution going on the basic characteristic information of a formulation’s key physical properties.

As the nature of each sticky formulation differs, it is impossible to suggest that one single coating could solve a multitude of sticking problems, so what was needed was a way of recommending the right PharmaCote coating for each sticky formulation as efficiently and as accurately as possible. Prior to the introduction of TSAR Predict, selecting the right coating was a lengthy process that involved extensive in-the-field testing, taking up valuable production time for I Holland’s customers. I Holland would manufacture several tooling stations with different coatings, which would be taken to the customer’s facility and tested in situ with the product. Through trial and error, I Holland was then able to recommend the most appropriate anti-stick solution for that formulation. From start to finish, this process could take up to six months, whereas with TSAR Predict, providing I Holland has the aforementioned information, a highly accurate recommendation can be made within just hours or days.

With its highly skilled engineers, I Holland already possessed eight years’ experience in the provision of effective anti-stick solutions at the start of the project and had kept a record of which ones were likely to work for a number of APIs and formulations. Although, as Rob has been keen to stress, simply looking at historical data was insufficient: “More advanced scientific research needed to be applied, formulaic chemistry backing if you like,” a role that was fulfilled by Professor Roberts and the School of Pharmacy team.

There is of course always the possibility that sticking is caused by something other than particle adhesion but — now possessing an impressive 10 years’ anti-sticking expertise — I Holland has a thorough understanding of all the parameters that could be responsible and takes these into account whilst using the mathematical model. “TSAR Predict is only as powerful as it is because of all the knowledge and data that’s gone into it and the scientific development of our PharmaCote coatings over the years,” stressed Rob. “It’s about interpreting the data that we get out of the model to make the right recommendation.”

The TSAR project staff studied and created data for numerous customers’ formulations, taking into consideration key factors attributable to sticking such as Van der Waals forces or molecular attraction, capillary action linked to high moisture content and static electricity as well as other parameters such as roughness of the punch tips, different materials/chemistries on the punch tips and deformation mechanics of the granules. The mathematical model was thoroughly tested by matching predictions with compression trials on an R&D press.

At the end of the project, I Holland ran blind trials, inviting customers to send formulations that had not been used in the initial compression trials. “One of these blind trials moved quickly to production and the customer’s sticking issues are no more, it’s a big success,” enthused Rob. “We saw it all the way through, getting a prediction and carrying out our own compression trials on an R&D press as part of the project, and now the customer’s tried the final solution in production and it works.”

Although it has only been a couple of months, TSAR Predict is already very much in demand. Since the webinar, I Holland has been inundated with prediction requests from potential as well as existing customers, running data through the model numerous times on a daily basis. According to Rob, TSAR Predict has quickly integrated into the day-to-day running of the business leaving little time for all-important R&D work, hence its planned adoption by the company’s CSG (Customer Support Group) over the coming months will be a welcome relief. “Our CSG stretches right across the business,” he proudly stated. “The team offers pre- and post-sale technical support, advising customers on coating selection, tabletting issues, tooling problems, maintenance processes, etc. A number of CSG staff will soon have access to the TSAR Predict model and be able to run ad-hoc predictions.”

As the service is so new, it is impossible to definitively judge/accurately assess its success rate. Once a prediction has been made, the process that normally follows is receipt of the order, manufacture of the tooling, delivery to the customer, before it being run through production and prompting a verdict. There are a number of orders to be manufactured and there are some tooling sets that have been delivered and customers are waiting to use them, although as Rob keenly pointed out: “Where they have been put to the test so far, we’ve had great feedback.”

An additional highlight of the TSAR project is that through the knowledge gained on the causes of sticking, another PharmaCote coating — PharmaCote CT — has been developed. Rob described it as “unique” owing to the fact that it works very differently to the other anti-stick coatings in the range. “It’s all in the manufacturing technique; we’ve surface engineered the actual punch tip face in conjunction with the coating to almost provide a two-in-one solution,” he said. “We tested a very early prototype as part of the TSAR project and were pleasantly surprised to learn it offered exceptionally low adhesion forces for the majority of formulations in the project’s compression trials.”

Looking as always to the future, I Holland intends to develop further anti-stick solutions that will be added to the model. As outlined by Rob, the TSAR project has paved the way for improving and extending the PharmaCote range to accommodate additional parameters. “The two-year project has taught us an enormous amount about particle adhesion, which will help us focus our development in the future,” he said. “We want to be recognised as a company dedicated to tabletting science, driving the development of advanced solutions in a direction that suits our customers.”