The technology used in continuous pharmaceutical manufacturing has matured even further in recent years. Within the scope of tablet production, one major focus is on direct compression, which combines a particularly lean plant design with process analysis technology. The FE CPS dosing and mixing unit sets new standards in the continuous direct compression process.
Key insights:
- Continuous manufacturing is a central development area at Fette Compacting – with a focus on continuous direct compression.
- On its way to becoming a finished tablet, the powder (or premixture) goes through several flexibly adjustable process steps: from the inlet ports for the materials to the outlet port for the mixture.
- The following steps ensure continuous product flow in tablet production: material feed, dosing, mixing process, inline quality control and conveying.
Technical process advantages mean that continuous manufacturing could soon assert itself as an alternative to the batch-to-batch process. Market research institutes are forecasting high growth of around 10% for the years to come. Regulatory authorities such as the Food and Drug Administration (FDA) consider the process to be an innovative, quality-driven tool for modernising the pharmaceutical industry.
Continuous manufacturing is a central development area at Fette Compacting – with a focus on continuous direct compression. In particular, this can be attributed to a wide range of applications which can be combined with plant design optimised in terms of space and resources as well as precise process analysis. Direct pressing entails feeding the powder from the dosing and mixing module into the tablet press without any additional granulation. Compared to granulation-based production, several production steps are no longer required, which is why spatial requirements are reduced and the process is leaner overall.
Further development via Quality-by-Design
Process chart: The starting materials are prepared for tableting in five process steps.
In an effort to further develop the continuous direct pressing process, Fette Compacting has been pursuing a Quality-by-Design approach for some years now which has also contributed toward a versatile process design. Ultimately, culminating in the FE CPS dosing and mixing unit. In combination with a rotary tablet press and a central operating panel, it forms a comprehensive continuous direct pressing line. The entire plant can be integrated on a single level in existing production rooms.
On its way to becoming a finished tablet, the powder (or premixture) goes through several flexibly adjustable process steps: from the inlet ports for the materials to the outlet port for the mixture, which is in turn connected to the inlet of the downstream tablet press. The continuous product flow can be summarised and described in the following steps:
1. Material feed
The dosing and mixing unit features up to six inlets for the material feed. Each inlet can be used for an individual ingredient or a premixture of several ingredients. A premixture is used when the total number of ingredients exceeds six or the concentration of an ingredient in the formula is particularly low.
Various sets of twin screws are available for feeding.
Each feeder is equipped with an automatic refill system (ARS) which feeds the material reliably and at consistent intervals to the next process step. As this first step is decisive for the correct operation of the line as a whole, Fette Compacting has developed its own refill system with special screws. These can convey very complex raw materials into the dosing process, both reliably and consistently.
2. Dosing
Dosing is at the heart of the new technology, so to speak. Up to six gravimetric (loss-in-weight, LIW) powder dosing units are used here. For each feeder, the concentration of the respective material in the formula is stored in the cross-plant product recipe. Combined with the required plant throughput, the control system automatically calculates the requisite flow rate. The LIW feeders use twin screws to feed material to the next process step with the required feed rate and minimal feed variability.
3. Mixing process
In the next step, a specially developed horizontal powder mixer is used. It has two successive but independent mixing zones – without a dead zone in between. This allows mixing processes with high and low shear energy to be combined in a single mixer and to achieve the best mixing results depending on formulation requirements. The mixer is equipped with four inlet ports: two in the first mixing zone and two in the second.
A special mixer combines mixing processes with high and low shear, as well as different mixing durations.
The various ingredients are directed from the LIW feeders to the mixer inlets using a combination of downpipes and transfer hoppers. Each specific hopper configuration determines which outlet of the feeder is connected to which mixer inlet. The mixing duration for the respective ingredient is thereby specified. Various hopper configurations are available as format parts, offering a great deal of flexibility. This enables users to achieve the optimal process setting of shear intensity and mixing duration for a wide range of recipes.
4. Inline quality control
Embedded process analytical technology (ePAT) can be used at the output of the mixer. A near-infrared spectroscopic sensor checks, among other things, the homogeneity of the mixed powder and the concentration of the active ingredient. In this way, the system can be permanently monitored, and quality deviations can be discovered without delay. Especially in process development, it is important to continuously record and optimise the mixing process. Further ePAT sensors are located at the tablet press, which enables continuous in-process monitoring at high speed.
5. Conveying
In the last step before tableting, the powder mixture is conveyed evenly and without the risk of segregation to the inlet of the tablet press. For this purpose, a powder transport system was developed, which conveys the product by dense phase conveying over a distance of up to ten meters without the risk of segregation. Via a conveying hose, it reaches the conveying arm of the FE CPS, which can be flexibly aligned with the inlet of the tablet press. This ensures that the thoroughly mixed powder reaches the tablet press without interference and is compressed in the usual quality. The mixing conveyor system also allows a two-room set-up of the direct pressing line: the FE CPS can be set up in one room while the tablet press is in an adjacent room. This can be interesting if the system is to be installed in an existing tablet production line.
In this combination, these process steps open up new perspectives for efficiency and product quality in tableting. Thanks to its lean plant design and a process analysis technology adapted to it, the FE CPS offers a compact yet reliable solution for continuous manufacturing.