Fluid Bed Granulating (Granulation)

There are a number of granulation technologies available to pharmaceutical manufacturers. Given the importance of granulation in the production of oral dosage forms, this paper offers advice on various process and looks at the implications of two different applications.

Granulation is one of the most important unit operations in the production of pharmaceutical oral dosage forms. However, there are many different technologies each having different strengths and weaknesses. Most companies choose which one to use simply based on their own experience.This article introduces different processes, compares them objectively and offers unbiased advice on the merits of each system. It then looks at the implications of selection on two different applications.

Granulation methods:

• Single pot
• Fluid bed top spray granulation
• High shear granulation/fluid bed drying combination
• Continuous fluid bed granulation
• Fluidized spray drying
• Pellet production line

General aspects of granulation

Comparison of granulation processes

Tables I – III provide a brief overview of the implications of particular granulation methods. All information shown assumes ‘normal’ products. Some special products may behave differently.

Production scenario 1

A dedicated plant for the production of 1000 tonnes of granules of a water-based formulation.
The amounts of granulation liquid are estimated as shown in Table I. Further, it is assumed that cleaning is required once a week for only a few hours because it is a dedicated installation; the plant is operated in three shifts for 5 days each week; and the plant achieves 20 productive hours per day and 200 productive days per year.

Working on these assumptions, 5 tonnes of granules must be produced per day.Table IV shows the results for the different production scenarios.To complete this table (for the batch machines), the batch times were evaluated.These are based on customers' experiences and calculations regarding the drying capacity of the different equipment. Some materials with special granulation/drying properties may achieve entirely different batch times. By calculating the number of batches per day, the required batch size of 5 tonnes of granules per day was determined. For the single pot option it was not possible to achieve the requested throughput using only one machine. For all continuous processes, equipment with the requested throughput is available.To include the necessary investment costs in the table is extremely complicated as this depends on many other factors in addition to the granulation equipment and needs, and must, therefore, be evaluated carefully, case by case.

Production scenario 2

Installation for the production of four different water-based granulated products, each with a capacity of 32 tonnes per year.
The amounts of granulation liquid are estimated as shown in Table I.The process length for each product should be 1 week. It is also assumed that cleaning must be done only at the end of each process, which means that Friday is not a productive day. Further assumptions are that the plant is operated in two shifts for 5 days each week and that the plant achieves 16 productive hours per day and 200 productive days per year.