Tackling Common Problems in Tableting and Tooling

This article provides an overview of I Holland's tableting science anti-stick research (TSAR) project, which the company is conducting in collaboration with the University of Nottingham in the United Kingdom. The TSAR project seeks to understand why certain formulations stick to tablet tooling, a major problem often encountered by tablet manufacturers.

Problems during tablet manufacturing often result in process downtime and higher operating costs. Some of these problems can be minimized or eliminated with proper maintenance and storage of tablet tooling. Pharmaceutical Technology spoke to experts at I Holland about the causes of common problems such as tablet weight variation, hardness or breakage issues, capping, picking, and sticking, as well as a seven-step process for tool care.

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I Holland representatives also discussed the company's research collaboration with Nottingham University's School of Pharmacy in the United Kingdom, which seeks to understand why certain formulations stick to tablet tooling, a major problem that is often encountered by tablet manufacturers. The aim of this joint project is to develop a predictive tool that will enable the identification of the best coating solution for formulation-sticking issues without the need of carrying out full-scale trial-and-error experiments with several anti-stick coatings.

Tableting science

PharmTech: What is tableting science?

I Holland: Tableting science is part of I Holland's core service offering. It encompasses many aspects of our R&D capability, including work with academic and technical partners on scientific research projects that help us to improve our understanding of why a punch or die performs well. For example, for years many tooling manufacturers have polished punches to an optimum mirror finish because they know it helps the punch to perform more effectively, but no one really understood why this was the case. Punch and die manufacturers are essentially engineering companies and often have a reluctance to become involved in wider tableting issues.

Our investment in tableting science will help tablet manufacturers to reduce expenditures that can be associated with poor tooling performance further down the line by eliminating many issues before the punch or die hits production. For example, 'sticking' is a major tablet-production issue that we are trying to tackle through our work with the University of Nottingham on the tableting science anti-stick research (TSAR) project. We hope to deliver a predictive tool that will remove the need to undertake expensive coating trials to determine the best coating solution.

Common problems in tableting

PharmTech: What are the common problems encountered in tablet manufacturing?

I Holland: There are many common problems encountered in tablet manufacturing. Some of the most common of these are listed below. Each of these problem areas may have several potential causes, but brief overviews of the main ones are summarized below:

• Tablet weight variation. The most likely cause of this problem is the extensive variation in punch working lengths, which can often be due to worn punches or sticking/picking that can cause granules to build up on the punch face and result in nonuniform punch lengths.

• Picking. Picking refers to when a compressed granule adheres to the detail (i.e., embossing) on the punch face. This problem could be due to inappropriate embossing design, worn tip faces, insufficient compaction force, or granulation issues such as excessive moisture or insufficient lubricant.

• Sticking. Sticking is defined as general granule adherence to the punch-tip surface. The same causes as for picking may apply. Additionally, inappropriate tablet profile may have an impact on inadequate tablet hardness and density.

• Capping. Capping is the laminar separation of the tablet body or cup and is often caused by air entrapment in the body of the tablet.

• Poor tablet definition (embossing). This problem could be attributed to poor embossing design (i.e., too small or too shallow), worn punch faces due to abrasive formulation, or excessive polishing.

• Tablet hardness/breakage issues. These issues are often caused by uneven punch lengths across a set, incorrect binding agents in the formulation, or capping due to air entrapment.

Other tooling related problems exist such as:

• Tool-handling issues

• Punch-tip breakage

• Punch-head wear

• Punch tightness

• Die-bore wear

• Tip wear by abrasion

• Corrosion

• Pitting/impregnation of punch-tip faces

Punch and die manufacturers should be able to provide training on these issues and how to solve them (1).

The seven-step process

PharmTech: What are the solutions to these problems?

I Holland: Depending on the exact causes of each of the problems previously described, there are several potential solutions. As a guide, following a simple seven-step process for tool care and maintenance can help to minimize the potential occurrence of most tableting and tooling issues (2). The seven-step process is a logically planned and professional approach to tooling maintenance and storage as summarized below:

• Clean. When tooling is removed from the tablet press, it should be thoroughly cleaned and dried to remove any oil or product residue, especially from difficult-to-reach areas such as embossing and keyways.

• Assess. Punches and dies should be visually inspected under magnification for signs of damage, wear, or corrosion, and to validate the cleaning process. This assessment will establish whether the production process is running well or not, thereby giving clues to problems with the tablet press or tooling itself and if any tooling maintenance is required.

• Repair. Light surface wear, corrosion, and damage on tooling can be repaired and polished to a useable condition. Worn tips can result in poor quality tablets and inferior embossing definition that can lead to picking and sticking. Repair should be carried out by well-trained and experienced maintenance technicians to ensure that the tooling does not exceed tolerance limits.

• Measure. Measuring is essential after repair to ensure that critical tooling dimensions have been maintained within an acceptable working tolerance. Measuring should be carried out at regular intervals even if repair has not been necessary, to check for natural wear during the compaction process. The essential measurement is the critical working length of the punch as it controls tablet thickness, weight, and dosage.

• Polish. Controlled, light polishing on a frequent basis will ensure that tools are maintained to a smooth finish, thereby helping to maximize tooling life and reduce problems such as sticking and capping.

• Lubricate. Lubrication is important to protect, preserve, and aid smooth operation of the tooling. A range of oils and greases can be recommended for different applications, such as preservatives, or for lubrication purposes.

• Store. Tooling storage and transportation should be specifically designed to maximize security and safe handling to minimize damage and deterioration.

Anti-stick research

PharmTech:Could you tell us more about the TSAR project, for which you are collaborating with the University of Nottingham?

I Holland: Since the launch of our PharmaCote range of punch and die coatings more than five years ago, I Holland has been increasingly called on to solve sticking issues within the pharmaceutical sector as tablet manufacturers realize that these problems can be eliminated without reducing product yield and investing in expensive magnesium stearate systems. The traditional way of troubleshooting a sticking problem would have been to supply a customer with a test set of tools containing many different punch and die coatings. A full compression trial would be carried out at the customer's site to ascertain the coating that would most effectively solve the sticking problem. This approach involves a significant investment for the customer in the tooling as well as in time.

The aim of the TSAR project is to develop a predictive tool that will allow us to identify which punch and die coating is most likely to solve these sticking issues, thus removing the need to carry out full-scale compression trials with all of the anti-stick coatings. The development of the predictive tool will not commence until we have gathered sufficient interaction data from many different excipients and active ingredients. This work is currently in progress as we are testing several samples supplied by our customers.

We aim to use newly developed multivariant analysis techniques linked to nanoscale surface chemistry and morphology techniques such as atomic force microscopy (AFM), time-of-flight secondary ion mass spectroscopy (ToFSIMS), Raman spectroscopy, contact angle measurements, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and laser profilometry. Once the data are gathered, we will use a principle component analysis tool to allow us to group the different excipients/active ingredients. Only after this process, will we be able to start the development of the predictive tool.

We are currently halfway through the two-year project and have spent the first year solely gathering data from various products supplied to us by different customers. The most utilized piece of equipment to date has been the AFM, which allows us to quantitatively map, at the nanoscale, adhesion on PharmaCote coated tablet punches using single drug/excipient particles. The low adhesion force measurements (nN) gathered within the AFM indicates the level of Van der Waals forces that are present. We are also changing the humidity and temperature within the testing environment to gather data on capillary forces that are present. Only when all the ingredients of the formulation are tested in this analytical way, do we move the formulation into a production environment and compress tablets using the same PharmaCote coated tooling.

This 'real world' checking allows the results of the analytical testing to be verified in a production environment and gives the customer the reassurance that they are purchasing the optimum solution for their specific problem. It cannot be stressed enough how each sticking problem is unique and can vary significantly from site to site, press to press, and product to product, which makes laboratory compression testing vital.

References

1. Eurostandard Educational Collection 2010 Edition.

2. T. Higgins, Pharm. Tech. 37 (2) 30–31 (2013).