Getting into shape
Fast, hygienic changes for efficient processes

At first glance, all tablet presses have to do is get the active substance into shape quickly and reliably. Only on closer inspection is their true versatility revealed. Developers are currently focusing on easy-clean machines to allow product changes to be speeded up.
The demands placed on modern tablet pressures have risen enormously over the last few years, not least due to trends in the general conditions for the pharmaceutical industry. The industry finds itself having to work more efficiently while remaining flexible, with frequent product changes and smaller batches sizes the norm. The performance of tablet presses has improved considerably in recent years thanks to progress in mechanical and electronic engineering. Not only can heavy-duty machines reliably deliver huge quantities of tablets, they can also handle new forms of administering drugs. In particular, the steady rise in the proportion of highly active agents in tablets, for instance, presents new challenges for the operation and degree of cleanliness of tablet presses. This has implications for occupational safety and reductions in workplace stresses, which is why containment for tablet presses is gaining increasingly in importance.

It was with this in mind that Fette presented the 2090i WiP with the Containment Package at last year‘s Achema show. The ‚WiP generation‘ now covers the entire spectrum with three machine types: the 1090i WiP for small batch runs, the 2090i WiP for medium-sized batches and the 3090i WiP for large batches. From experience gained through the use of WiP presses, cleaning times can be over 50 per cent shorter than conventional cleaning, depending on the product. This benefit is joined by lower costs thanks to the simpler room configuration, the lighter protective clothing needed by operators and savings resulting from shorter change-over times. And Fette points out one further aspect: with less time now being required, WiP cleaning is now financially viable even for non-toxic products. The minimization in down times achieved so far due to the interchangeable rotors will be reduced still further. As regards safety enhancements, Fette‘s wireless terminal should also be interesting. The positioning of the terminal, now spatially separate from the machine, ensures that the tried-and-tested characteristics familiar to the press operator are retained. The workstation at the terminal is cleaner and free of dust, while the noise level outside production has been significantly reduced.

Tablet presses for R&D

Over at Korsch in Berlin, they‘re convinced of the advantages of WiP technology. These include reduced down times thanks to a 50 to 70 percent cut in cleaning times and a much improved, reproducible and qualifiable cleaning result. The Berlin supplier uses WiP technology both for the XL 400 for normal one-layer tablets and for the XL 400 in the two-layer form. All the strict archiving requirements of FDA 21 CFR Part 11 regulations are met because all cleaning operations and cycles are controlled, stored and documented automatically. This means that the very highest requirements for machine cleaning are observed, particularly when highly active and toxic substances are used. The WipCon, a manually washable tablet press with a hand spray in the isolator and gloveboxes, has recently been developed specially for the purposes of protecting operators handling highly active products. The tablet press takes up little space and is easily moved, allowing it to be integrated seamlessly into existing systems. It was designed for small quantities of up to one kilogram, such as those that might occur in the lab, and for small batch runs. The Integrated Pharmaresearch tool, an integrated system enabling all data to be collected and analyzed, is available as an option. This tool, say the Berlin developers, opens up new possibilities for product development.

Quick and easy changes on the fly

For Kilian/IMA too, the ease of cleaning is a decisive criterion. On the Synthesis tablet press the upper compression rollers are attached to pivoted brackets, enabling them to be swung out easily. This simplifies both maintenance and cleaning, but the ease of movement is also essential when the mold plate needs to be changed. The latter can be used for cleaning and when changing the tool type. The production area is completely isolated from the mechanical area by special seals and bellows, preventing any product dust getting into the mechanism. The tablet outlet and the fill shoe are mounted on pivot pins and can be swung out. This allows optimum access to the production area while at the same time responding to the need to make maintenance and cleaning work easier, runs the argument.

Rapid transfer from the lab to production

The rapid exchange of tools is particularly attractive for small and medium-sized businesses. Courtoy recently presented its tablet press module with an additional component called D-ECM, conceived for R&D formulations and the production of clinical samples. The concept allows systems to be changed over to a new product within 30 minutes. The D-ECM module contains all parts that come into contact with the product and can be removed from the machine in one piece, thus avoiding contamination. The D-ECM can be cleaned offline and is able to produce batches of up to one kilogram with minimum product loss.

Manesty‘s Xpress series has also long been a fixture on the market. The Xpress 300 was designed for the cost-effective production of small and medium runs or optimization of the transition from the development and clinical test phase to production. A selection of six interchangeable turrets enables tablet size and discharge to be optimized. According to the manufacturer, the turret can be exchanged quickly and easily using just one single tool. The stepped housing construction ensures the complete separation of product, manufacturing and electrical areas, guaranteeing effective cleaning for rapid product changes without any need to replace the turret. .

PAT brings improvement in
manufacturing output

The FDA and other regulatory authorities are currently encouraging the pharmaceutical industry to make use of Process Analytical Technologies (PAT). PAT is a system for developing, analyzing and controlling production processes through the repeated measurement of critical qualities and performance attributes of raw materials, intermediate products and the processes themselves with the aim of enhancing the quality of the end product. It is crucial that the term ‚Analytical‘ is interpreted very widely and that it is also taken to include mathematical, chemical, microbiological and physical methods and risk analyses. A PAT system will vary from one product to another and should cover the entire product development process. This includes process analysis, optimization of the process and the product and implementation of an extended process control. The implementation of a technical solution for the inline control of products is just one small part of a larger analytical system. This is where NIR (Near Infra Red) technologies, spectroscopy, X-rays and acoustic analyses have come to the fore in recent times. To satisfy customer demand, IMA has already equipped some of its tablet presses with an NIR system so as to control the uniformity of the tablets.

Fette, too, has realized the integration of analytical components in tablet presses and peripherals. Examples include measurement of the pressing force within the press, determination of the weight, hardness, diameter and thickness and external analysis of the active agent in the periphery. The results of these tests flow directly into the control of the process. Fette already meets today‘s FDA standards and has taken a decisive step further into the control systems.

Manesty also offers a range of modular control systems for the automated control and monitoring of tablet production. They include control and analytical systems for use in research & development and in production. One of these measures the pressing force and tablet weight. This reduces wastage, increases output and improves process reliability and tablet quality.

Reliable control even at high speeds

It is still the case, though, that examination of the tablets produced puts users in
a quandary. Until now, experts have not thought there was any machine that could check the individual tablet weights at the same speed. If discrepancies in weight
between two random samples are found, the practice so far has been for whole production batches to be rejected. Now, though, KKE 2500, the new tablet weighing module from Bosch Packaging, allows individual tables of such batches to be reweighed for greater production reliability. The advantage is that tablet wastage is minimized and production efficiency is boosted. Tablets are sorted accurately at a speed of up to 60,000 tablets per hour.
To conclude, the developments outlined here demonstrate that topics such as high containment, PAT, process reliability and performance boosts are key issues for users and developers alike. müh