The essentials of wet granulation

Tobias Borgers discusses the optimal application for compact granules

Granulation plays an important role in oral solid dosage (OSD) production. It 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 enough strength. Granules can be used directly as pharmaceuticals or can serve as an intermediate in the production of tablets or capsules.

Normally, the following four granulation methods are used in the pharmaceutical industry: fluidised-bed granulation; high-shear granulation; single-pot granulation; and twin-screw granulation, which is a continuous process by design. 

High-shear wet granulation is a shaping process for granulation that has been successfully used by the pharmaceutical industry. The granulators are used for several applications in the pharmaceutical, nutraceutical and agrochemical industry or to produce pet foods. In general, High-shear granulators can be divided into two classes – granulators with horizontal axis and vertical axis.

Key elements of the high-shear granulator are a closed process bowl with an impeller and chopper. The dry powders are mixed by the rotating impeller before a liquid binder is added. So, the impeller produces high-density granules and guarantees effective and fast granulation. The chopper prevents excessive granule growth (breaking up any granules) and distributes the granulation fluid throughout the product. The granulators, from laboratory to large production scale, provide best conditions to produce high-quality pharmaceutical products in short times.

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 that can be removed by drying.

Originally used only as a dryer after a wet granulation process, it replaced the step wisely with classical oven drying. 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.

Fluidised-bed systems can be classified as top spray, bottom spray and tangential spray systems. In the top spray systems, the nozzles were mounted on the top to spray onto the wet particles. 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). The most promising change was the development of the 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.

An ideal combination

The combination of both established processes high-shear granulation and fluidised-bed dryer promise cost reduction and great potential in daily production. The minimised design of compact granulation modules ensures optimal results and features a high-shear mixer and fluid bed dryer side by side, with sieving step in between.

One important advantage of the implementation of this combination in modern facilities is the reduction of the required total size. By installing both machines next to each other, not only the width can be reduced, but also the installation height is very low. Furthermore, the required space for technical components can be reduced.

Optimisation of classic wet granulation due to technological advantages

In addition to technical advances, improvements in the sector of safety have been made. The high-shear granulator and conical sieve, including the transfer pipe, is shock pressure resistant up to 12 bar. Consequently, all equipment parts in contact with dust or solvents (if required) are designed for shock pressure resistance.

When it comes to how traditional wet granulation can be realised efficiently, economically and ergonomically, the compact granulation module is a compelling solution.

Twin-screw granulation (TSG) is an established method for continuous wet granulation and is seen as the starting point by companies when it comes to the continuous manufacturing of pharmaceuticals. The powder to be granulated is fed onto two screws, which rotate in the same direction in a cylinder, thereby transporting the material through the process zone and kneading and mixing it at the same time.

This TSG design results in several advantages, including short dwell times for the material in the process; fast and efficient reactions to process and quality deviations; and space-reduction in the required footprint of the machines and associated GMP areas. It also offers mixing and granulation in one step in the shortest time possible as well as 100% in-line quality control.

Due to the flexibility and simple implementation of the process, the TSG is the ideal machine for continuous manufacturing processes in R&D and production with a high potential.

Tobias Borgers is with L.B. Bohle

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