In the pharmaceutical industry, granulation plays a key role in the production of solid dosage forms – particularly due to the pressure of rising costs. Granulation aims to form coarser agglomerates from fine powder. Agglomerates may consist of fixed, dry grains, and each grain is an agglomeration of powder particles of sufficient strength. Granulates can be used directly as pharmaceuticals or can serve as an intermediate in the production of tablets or capsules.
L.B. Bohle Maschinen + Verfahren GmbH (Ennigerloh) offers a wide range of granulation solutions. The Bohle portfolio for manufacturing oral solids includes complete production systems as well as stand-alone machines. In addition, the mechanical engineering company specialist has developed and delivered a large number of containment applications for the pharmaceutical and food industries. An introduction to granulation concepts, fields of application and added value for customers is given below.
Continuous dry granulation is a well-established process in the pharmaceutical industry and is used for more than just moisture- or temperature-sensitive products. Compared with wet granulation, no energy-intensive drying processes are required. This reduces the need for large investments in equipment and production facilities and results in a lower cost per batch. Because no drying is required, no solvents need to be stocked, extracted or disposed of.
Dry granulators ensure a compacting process with high material throughput. A single plant can produce different products and batch sizes.
Dry granulators are distinguished on the basis of their roller arrangement. Types include horizontal, vertical and inclined rollers. The press rollers also vary in width, diameter and surface texture, and there is a choice between fixed or variable gaps. Dry granulators with a variable gap are preferred due to the fact that they ensure consistent granule porosity at a constant pressing force.
Bohle’s BRC series combines a high level of product capacity with minimum material loss. This system outclasses rival solutions by generating force through purely electromechanical means to ensure consistent ribbon properties. The BRC uses highly innovative methods to regulate compacting force and ribbon thickness. It compacts material uniformly over a production range of <1 - 400 kg/h. The sophisticated system design facilitates the handling and shortens the assembly process.
The hygienic design and the integrated washer nozzles, fitted as standard, allow for an effective WIP process. Even at high material throughputs, the cone-shaped Bohle Turbo BTS sieve mill and sieve inserts gently crush the ribbons into granules with the desired particle size distribution. Each BRC can be mounted with a different rotary sieve within minutes to adjust to new process and ribbon requirements. Thanks to its functional GMP-compliant design and PAT tool support, the compactor meets the requirements of the pharmaceutical “Quality by Design”.
High-shear mixer granulation has been used in the pharmaceutical industry for many decades. Mixing, high-shear wet granulation and drying (vacuum drying, carrier-gas drying, or drying by microwave heat) are all carried out in one container.
Mixer granulators offer the following benefits:
- Secure production within a closed container in a vacuum
- High mixing and granulation efficiency (even for low doses of active agents at < 1%)
- Drying at low temperatures
- Small product contact surface for fast, easy cleaning and fast product changeover
- Efficient solvent recovery through cooling water
- Compact footprint for low space requirements
The VMA product range includes classic mixer granulators with agitator and chopper units and a top-drive system. Two stirrers produce a shearing action and loosen the product. This helps to prevent clumping and ensures that the resulting granulate is of optimum quality. At the heart of the VMA is the GMP-compliant, double-sheathed process tank. The main aggregates are integrated in the lid of the pelletizing pot (top drive). The process tank is emptied through a cone-shaped sieve (BTS 200) via the floor outlet into a container (IBC). Formula-controlled cleaning is carried out automatically. The VMA produces batch sizes from 20 to 960 litres and can be installed in potentially explosive environments.
Fluidized Bed Granulation
Fluidized bed systems have been used in the pharmaceutical industry for many decades. Adding an aqueous or alcoholic granulation medium compresses the mixture of dry powder particles. The fluid contains a volatile solvent which can be removed by drying. For a long time, fluidized bed solutions were dominated by top-spray systems, however the benefits of systems with tangential spray nozzles are becoming more and more apparent, and these systems now tend to take over from top-spray granulators. Since the fluidized particles or granules move tangentially at relatively low fluidization height, they do not require a high-volume expansion. This reduces the required installation height, saving cost and production space. Another advantage of the tangential design in plants from L.B. Bohle is that granulation, coating and drying can be carried out in a single system without alteration of equipment setup.
In its fluidized bed system BFS, L.B. Bohle uses tangentially mounted spray nozzles and the patented Bohle Uni Cone BUC®, a specially slotted air distributor plate with a conical displacement cone for batches of 1 to 500 kg. Its pressure shock resistance of up to 12 bar makes the BFS the ideal choice for organic methods. Short product transfer times and efficient cleaning procedures offer additional potential savings in production time and cost. The geometrically similar structure simplifies scaling-up.
A newly developed, protected multi-purpose valve directly above the distributor plate facilitates the dust-free suction and draining of the product container. Its clear benefits with regards to ergonomics and cleaning make the BFS stand out from other fluidized bed systems on the market.
In addition to these three featured system types, L.B. Bohle also provides high-shear and twin-screw granulation systems as well as a compact system consisting of the high-shear granulator GMA, wet sieve, fluidized bed system BFS, cyclone separator and dry sieve.