Market Challenges

First, the pharmaceutical industry has seen a significant shift of investments in solid dosage production equipment towards generics and contract manufacturing. As the companies in this segment of the market are, by nature, strongly focused on cost reduction, great emphasis has been placed on productivity, flexibility and process yield (that is, minimal product loss). Equipment cost and reliability, as well as fast on-site assistance have also become key selection criteria. Research and development-based companies have also been forced to follow this cost reduction trend.

Secondly, the meteoric growth of new pharmaceutical markets in the Middle East and the Far East (India, China and South Korea, for example) has resulted in investments in solid dosage equipment in these regions to surpass the investments made in North America and Europe. This puts an increased pressure on equipment price and has resulted in several Western based companies moving the design, manufacture and assembly of their equipment to Asia.

Finally, with the increased potency of new APIs, there is a growing need for better protection of the operator against the effects of pharmaceutical product processing. Operator exposure can be reduced either through the use of Personal Protective Equipment (PPE) or by making the equipment highly contained. The latter approach is the preferred solution, primarily for ergonomic reasons and because it offers a more efficient way of protecting the environment in general, as well as the facility and other personnel.

Technology Breakthroughs

Although the operating principle and fundamental design of the rotary tablet press have not changed for decades, multiple machine design improvements have been developed and implemented by various suppliers to reduce cost and lead time; and, more importantly, to increase productivity, flexibility and safety performance.

The initial emphasis of innovation was on reducing the amount of time required for machine cleaning and product changeover. The first significant change was the “exchangeable turret,” introduced to the market by Fette in the early 1990s and now available from nearly all suppliers. Although this machine feature offers great flexibility with regard to the tooling types that can be used on the same machine, the time saved for cleaning and format changeover is limited; after removal of the turret, the complex inside of the tablet press still needs to be cleaned. Therefore, openness of structure and accessibility were further improved (such as the XL range by Korsch). Taking a different approach to the challenge, IMA came up with a revolutionary design without an exchangeable turret, but with centrifugal die filling and Clean-in-Place capability. Whilst in early 2000, GEA introduced the “Exchangeable Compression Module," a concept that made extremely fast product changeover possible thanks to off-line cleaning, and also offered an increased level of dust containment compared with conventional removable turret machines.

In more recent years, various machine design improvements have been made to increase the instantaneous output of tablet presses. To achieve this, it was necessary to enhance the efficiency of the forced paddle feeders to guarantee uniform die filling — and consequently tablet weight stability — at these higher outputs. The next step was to increase the number of punch stations on the turret (the die plate segments by Fette, for example; the exchangeable die disc with die shells by GEA) and/or to increase the rotation speed of the turret. When increasing the RPM of the turret, the compression dwell time for each individual tablet shortens, often resulting in insufficient hardness, capping or lamination. Methods that have now been developed to maintain a longer dwell time include air compensation and, to a lesser extent, larger compression rollers and punches with special head design.

The last 10 years have also seen a significant effort to design complete tablet production lines to handle potent and toxic drugs. As the powder in-feed, tablet handling, sampling and tablet collection all have to be performed under “high containment” conditions, it became imperative to design complete lines integrating the peripheral equipment, such as the powder discharge station, tablet deduster, metal detector, dust extractor and tablet analyzer. Initially, the most common technique was to build isolators around the equipment and provide Wash-in-Place capability. However, the latest design trend is toward containment at the source and off-line washing, as these concepts allow equipment to be smaller, easier to install and operate, and lower priced.

Drawbacks

The main shortcoming of modern tablet presses is their lack of advanced process control. Most tablet presses are equipped with only one feedback control loop, which is based on main compression force measurement as an indirect estimation of tablet weight. Remedying this loop is achieved through tablet sampling: 20 tablets every 15–30 minutes are sampled while the machine runs at 200,000 tablets/h. This naturally calls into question the statistical relevance and accuracy of this method. Only very few new methods of process control and new types of sensors are being offered for on-line monitoring and controlling of other tablet CQAs, such as hardness, API content and dissolution time.