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Continuous Manufacturing – Continuous need not be complex

The success of a Continuous Manufacturing line is primarily dependent on its PAT (Process Analytical Technology) system. With the right concept, users can ensure that all relevant parameters are recorded and sensors are integrated smoothly in the overall process.


Dr. Anna Novikova, PAT-expert at Fette Compacting, explains what needs to be complied with for continuous tableting.

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Dr. Anna Novikova, Pharmacist and PAT-expert at Fette Compacting


Dr. Novikova, what parameters are critical in continuous operation?

That depends on the individual process steps. If, for example, a mixer is used, the user needs to take particular care with mixing homogeneity. Base materials must not separate again afterwards. During granulation, for example, the distribution of particle sizes plays a key role. Where wet granulation is involved, the residual moisture must be kept at a constant low. All of these factors need to be recorded by sensors, measured, monitored and adapted, if necessary. The general rule of thumb is: The more slim the press design, the easier the process control. Which is one of the reasons why we focus on direct compression. We also anticipate demand for this process to continue to grow.

What are the advantages of direct compression?

The powder is fed from the mixer into the tablet press without being granulated. This eliminates an entire process step which would require additional energy and time in the case of wet granulation, because it requires drying. This is compounded by the fact that each process step also needs to be developed beforehand. Direct compression, therefore, shortens the development time. We regard the process as the right manufacturing course for many formulations.

What disadvantages are there?

Preliminary treatment may be required based on the flow properties, adhesive forces between the particles, and other factors of the active ingredients and auxiliary agents. The first step always involves examining whether direct compression is even possible. Within the framework of Continuous Manufacturing, it is important how the tablet press is integrated in the process as a whole. This determines the efficiency of production and the quality of the tablets. We have already tested many different scenarios with great success. We can recommend direct compression as a continuous process – whenever possible from a material perspective. Our FE55 tablet press is tailored for these tasks and its three compression stations permit processability, i.e. direct compression, of materials.

Can you give us an example of a test?

Recently, we conducted tests with a customer in our Competence Center in Schwarzenbek. This involved direct compression on an active ingredient which is classified as a pharmaceutical in some countries. So it was extremely important to achieve and document an exact concentration. At 0.3 percent, it was to be extremely low, representing a complex task. Using the appropriate PAT sensor technology, i.e. Raman spectroscopy in this case, we were able to accurately measure the active substance.

What does “Raman” mean and what other measuring methods are there?

Let’s approach this in reverse: in most cases, roughly 90 percent, we use near-infrared spectroscopy, also referred to as NIRS. The advantage with this is that many active substances react well to its spectral range and the rays can penetrate deeply into the tablet without damaging it. Furthermore, NIRS is fast and therefore optimal for highperformance machines. However, it reaches its limit when there is an active ingredient content of less than one percent. This is where Raman spectroscopy comes in as a very strong laser is used. And it is less sensitive in terms of process variations, but requires operating experience to prevent over-layering by fluorescence, for example. In special cases, we also rely on methods such as laser-induced fluorescence (LIF ), UV or Terahertz spectroscopy.

Where are the measuring points located in the press?

The number of sensors varies depending on the respective application. A sensor is often used after the mixer, before the powder reaches the tablet press, and sometimes at the Fill-O-Matic. We examine the chemical properties of the finished tablet either in-line in the tablet press or at-line in the Checkmaster. The latter is also coupled with physical measurements of weight, size and hardness. What is critical is that the inter- play of measurement processes and measuring points is right. Enabling the sensors – the eyes of the continuous system – to see best.

What are the next steps involving Continuous Manufacturing?

We are working with various partners on standardized PAT tools for continuous operation. We implement the range and know-how in our Competence Centers enabling customers all over the world to benefit from the turnkey machines and software solutions for continuous operation.

Please do not hesitate to contact us if you have any queries.

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