Manufacturing
Granulation in Pharmaceutical Technology
Flexible and Efficient Applications for Solids Production Granulation plays a key role in the production of solid dosage forms in the pharmaceutical industry. Particularly due to the pressure of rising costs, fast and efficient granulation processes are becoming increasingly important. 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. Granules are used directly as pharmaceuticals or can serve as an intermediate in the production of tablets or capsules. Beside wet granulation, which is the oldest and most common granulation technique and can be accomplished using different types of equipment, dry granulation is becoming more and more famous. The German Technology Company L.B. Bohle Maschinen und Verfahren GmbH (Ennigerloh) offer 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 many containment applications for the pharmaceutical and nutraceutical industries. This report gives a first introduction to the different granulation techniques and names some product examples. Dry Granulation Continuous dry granulation or roller compaction is an established process in the pharmaceutical industry and is required when wet granulation may be unsuitable as a manufacturing method. Roller compaction 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 by reducing the energy costs. Because no drying is required, no 92 INTERNATIONAL PHARMACEUTICAL INDUSTRY
solvents need to be stocked, extracted or disposed of. Dry granulators ensure a compacting process with high material throughput. A single machine can produce different products and batch sizes. Roller compactors are distinguished based on 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 because they ensure consistent granule porosity at a constant pressing force. The aim is to process the powder’s freeflowing granules with a defined density or porosity that allows for immediate pelletising after compacting. The powder is compacted between two rollers with specified gap widths. The impact on the rollers, as well as the gap width, is monitored via sensors and there is also the option to install process analytical technology (PAT). All data are integrated into a control circuit to ensure continuous process quality, while an electro-mechanical drive provides precise and fast control. The chopper unit below the compacting rollers processes flakes into a granule at a defined granular size, and the unit is equipped with a conical sieve with replaceable inserts for different particle sizes. Even at high material throughputs, the coneshaped sieve and its inserts gently crush the ribbons into granules with the desired particle size distribution. Each Bohle BRC can be mounted with a different rotary sieve within minutes to adjust to new process and ribbon requirements. L.B. 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 controls the compacting force and ribbon thickness very innovatively. It produces the even compacting of material 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 washing nozzles, fitted as standard, allow for an effective WIP process. Thanks to its functional GMP-compliant design and PAT tool support, the compactor meets the requirements of the pharmaceutical “quality by design”. Fluid Bed Granulation Fluid bed granulators and dryers 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. Originally used only as a dryer after a wet granulation process, it replaced step-wisely the classical oven drying in pharmaceutical production. Today, fluid bed drying can still be considered state-of-the-art within pharmaceutical drying processes. With the additional implementation of spray nozzles, fluid bed dryers became fluid bed granulators - thus wet granulation could be smoothly performed in one discrete device. In these applications, the nozzles were mounted on the top in order to spray onto the wet particles (top spray setup). Further development used the same apparatus for coating of tablets or other particles with an additional insert, whereby the spray nozzles were placed at the bottom of the fluid bed (bottom spray setup). This type has been used for decades in the pharmaceutical industry. The most promising change was the development of the fluid bed apparatus with tangentially mounted nozzles. The benefits of systems with tangential spray nozzles are becoming more and more apparent and these systems are now tending to take over from top-spray granulators. Since the fluidised particles or granules move tangentially at relatively low fluidisation height, they do not require a high-volume expansion. This reduces the required installation height, saving costs Spring 2021 Volume 13 Issue 1
