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Rob Blanchard and Clive Roberts discuss the issues surrounding tablet sticking.
Earlier this year, I Holland and the UK's University of Nottingham launched a two-year Tabletting Science Anti-stick Research project. One particular issue that will be investigated is what makes formulations stick to tablet tooling surfaces, including why certain coatings resist sticking, whereas others do not. With sticking being an important issue facing tablet manufacturers, Pharmaceutical Technology Europe spoke to Rob Blanchard, Research and Development Manager at I Holland, and Clive Roberts, Chair of Pharmaceutical Nanotechnology at the UK's University of Nottingham and Director at the Nottingham Nanotechnology and Nanoscience Centre at the University of Nottingham, to find out more about the collaboration.
Q: What issues can tablet sticking cause during pharmaceutical manufacturing, and how well understood is this problem?
Sticking is a complex phenomenon created by different parameters such as Van der Waals forces, capillary action, electrostatics and the surface roughness of the tablet tooling, to name but a few. Sticking can reduce yields, double compression (causing damage to tablet press and tooling), and cause poor tablet appearance, inconsistent tablet dosage and inconsistent tablet hardness, as well as other production issues. Sticking should not be confused with picking, which can look very similar to sticking, but which can commonly be resolved by changing tablet design. In recent years, I Holland has seen increasing requests for assistance in solving sticking from both generics and pharmaceutical companies alike.
Q: How do manufacturers currently address the problem of tablet sticking? Has the issue influenced the development of any new tools and technologies?
A common way of reducing sticking is to slow the tablet press down, thus increasing the dwell time. However, this solution is unpopular with tablet manufacturers because it reduces productivity of the tablet press. As a consequence, tablet press manufacturers and tablet tooling manufacturers have introduced solutions to help the end-user reduce sticking issues in production. For instance, I Holland has developed a range of antistick coatings that have been successful in solving sticking, but the coating used should always be matched to the specific formulation. In the past we have worked in partnership with our customers to carry out trials using all the antistick coating solutions in order to match the correct coating with the formulation and environmental conditions. A potential issue with this method is the associated cost incurred in time and expense to find the correct solution.
Q: With a variety of ingredients used in manufacturing, it must be difficult to systematically benchmark sticking behaviour for each ingredient. Can you talk about how the new collaboration between I Holland and the University of Nottingham aims to tackle this issue?
This is an important question and is in fact also complicated by orientation effects because the same material (if crystalline) can present quite different surface properties (chemical and mechanical) depending on preferential orientation effects. However, whilst building a library of data will take time, the range of excipients used in most formulations is not actually so extensive with the same materials (albeit in slightly different forms) often being used, particularly, with the high percentage content of solid dosage forms. Of course, APIs will be different and we will deal with the ones known to cause the most problems first and attempt to cluster compounds that have similar properties. Ultimately, the intention is to have a model that can predict sticking to various punch surfaces not based upon complex analytical measurements, but on a limited set of parameters that may largely already be known.
Q: What techniques are necessary to further examine the intricacies of tablet sticking? How will the results of these techniques be combined to increase knowledge?
The project is exploiting a range of advanced surface analytical techniques to derive chemical and physical data from drug and excipients particles. The work also involves quantitatively mapping adhesion at the nano and micro scale using single drug particles, and links this adhesion data to actual tabletting experiments utilising a range of novel and controllable surface coated tablet punches with well‑defined characteristics. Multivariate analysis and principal component analysis will be used to identify the parameter(s) that influence sticking to form the basis of a model to predict propensity for sticking, based upon these factors. The ongoing use of the advanced techniques employed to collect the data in this research should not be required to implement this prediction in a commercial environment.
Q: Are there any particular areas that the collaboration will focus on?
Previous research has focused on only a few excipients and therefore did not allow a predictive tool to be developed that would allow selection of the correct coating without the need of expensive and time consuming compression trials.The aim of I Holland’s research and development team is to speed response times to solving customers’ problems, ultimately offering better customer service.