Homogeneous Product Quality Thanks to Fluidized-bed Technology What Really Matters with Fluidized-bed Technology

A guest post by Michael Benjamin, Head of Pharmaceutical Laboratory, Diosna Dierks & Söhne GmbH

Fluidized-bed systems combine a number of different advantages. The free movement of particles during fluidization leads to a larger contact surface area with the process air and with the granulation liquid. Operators benefit from good heat transfer, efficient drying, and good mixing. Different approaches to doing this are available.

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Fluidized-bed system in the Diosna Processlab
Fluidized-bed system in the Diosna Processlab
(Source: Diosna / Seidenglanz Images)

The key components of a fluidized-bed system are the fluidized-bed processor, a process air treatment system, and the exhaust air treatment. In order to control the process as closely and precisely as possible, the process development also focuses on optimized airflow and efficient feeding and emptying concepts. This is the only way to guarantee high yields, fast processes, and reproducible quality of the end products.

How does it work? In order to fluidize the product, the process air flow is direct from underneath through the distributor plate. The tangential air flow from this unit ensures uniform product movement and effective energy utilization. In spraying processes, this delivers homogeneous product quality. Before the process air leaves the system, it is purified via an integrated filtration system. Different alternatives are available for this, with single-chamber, dual-chamber, and cartridge filter systems available.

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Depending on the application, static redundant backup filters, cleanable filtration systems, or a cycle operation setup with solvent recovery can be used for the downstream exhaust air treatment technology.

The process determines the shape of the particles

The operating principle of the fluidized-bed method influences the resulting granulate and also has an impact on the process. For example, spray-granulation can be implemented either as a top-spray system or as a tangential-spray system, while the bottom-spray method is used for coating of pellets and mini-tablets. Each of these methods offers advantages and disadvantages. The top-spray method produces a more porous and finer granulate, but with a less regular shape. Top-spray granulation also requires higher spray nozzle pressure (at least 0.75 bar) due to so-called "bearding-effect" (i.e. product adhesion on the nozzle). But, in contrast to the bottom-spray method, this is offset by the fact that this method is less dependent upon the flow characteristics of the powder supply. In addition, the bottom-spray method produces a coarser granulate.

One of the advantages of the tangential-spray method is the reduced time required for the granulating process. The granulation liquid is added via a binary nozzle, which is arranged tangentially to the bottom part of the wall of the material container. As a result, not only is the granulating solution sprayed into the area where the powder particles are moving at their highest speed, but this is also the area with the longest drying path on account of the circulating movement of the product. As a result, significantly higher spray-rates are achieved (30 percent higher) thanks to the increased efficiency of the drying process. Spraying times are shorter and drying efficiency is dramatically improved. In addition, the tangential method is less sensitive to over-moistening of the granulate. Furthermore, a smaller amount of granulation liquid is required in order to achieve a particular target particle size. The tangential-spray method can help to produce coarser granulate. During the process it is possible to influence the desired properties via the pressure of the spray nozzle (droplet size). For example, lower pressure at the spray nozzle leads to a coarser granulate.

Parameters that influence the process

In addition, there are also a number of other aspects that should also be considered or can play a significant role in the process. For example, it is important that the apparatus is shock pressure resistant and that certified safety concepts are applied. Processes should take place in a way that is both reproducible and automated, and set-up times should be kept short.

Special containment rules apply in the case of highly active substances, in addition to which comprehensive cleaning concepts from WIP to CIP need to be incorporated. It goes without saying that an in-line quality control system, for example an integrated PAT system, and compliance with pharmaceutical standards in accordance with GAMP 5 should be basic requirements.

Further parameters that influence the process include e.g. the inlet-air temperature. The higher this temperature, the finer the granulate will be. If this temperature is reduced, then the process will yield a coarser granulate at the same spraying rate. Increased humidity of the air will also produce a coarser granulate, but the resulting drying times are longer.

The position of the nozzle also plays a decisive role. In the top-spray method, the optimum nozzle height should cover the surface of the bed. If the nozzle is too close to the fluidized-bed, the bed will still be fully wetted, but this will result in a coarser granulate. If the position is too high, the binding agent will dry before it reaches the powder particles (spray drying effect) and finer agglomerates will be produced as a result.

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In addition, it is a standard rule that the higher the atomization air pressure, the finer the droplet size. The same applies to the nozzle size: the larger the nozzle size, the larger the droplets (at the same pressure).

Improving production safety and reliability

As this handful of key points already shows, a great deal of experience is required to keep all aspects of the fluidized-bed process perfectly balanced and ensure that the properties of the final product are optimized. As well as looking at technical safety and reliability, it is also vital that the process is safeguarded. Only if the airflow, feeding and emptying concepts, and the granulating process are all perfectly coordinated with each other it is possible to ensure that high yields, fast processes, and reproducible quality of the end products can be ensured. This is why Diosna offers a broad range of components all around the CAP fluidized-bed processor. These include granulation liquid containers, cleaning stations, screen mills, lifting columns, and vacuum conveyor systems. All components of the equipment can be integrated in the overall control system, which also plays an important role. Diosna develops the necessary hardware and software solutions for this in-house on the basis of recognized standard systems. The software used is compliant with the requirements of 21 CFR Part 11 and offers extensive options for batch data acquisition and documentation. This also includes the PAT technology. Last but not least, intuitive user guidance and a phase-based recipe creation system deliver safe and reliable operation of the system – keeping every aspect of the entire fluidized-bed process in perfect balance.

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