Quasi-continuous granulation and

A QUASI-CONTINUOUS GRANULATION AND DRYING PROCESS (QCGDP) TO AVOID SCALE-UP PROBLEMS... 

Goals of the Quasi-Continuous Granulation and Drying Line... 

Constant values and reproducibility of the process are important facts of quasi-continuous granulation. The tests also show equal or better quality of granules and tablets, compared to common granulation equipment (Diosna P-600 high-speed granulator). 

In order to combine the advantages of a batch type and continuous production, a prototype for a quasi-continuous production line was developed (15-18,33-35). The principle of this quasi-continuous production line is based on a semi-continuous production of mini-batches in a specially designed high-shear mixer/granulator which is connected to a continuous multicell-fiuidized (Glatt Multicell ) bed dryer (Fig. 10). 

Due to this principle, a batch B defined for quality control purposes consists of a fixed number of n mini batches (subunits), i.e., B=nb.Thus, a tight in-process control of the mixing/granulation (6-9) and drying step (14) provides an excellent batch record of the quasi-continuous production of granules and an excellent opportunity for a continuous validation of the process and the equipment (14-18,32-34). 

Thus, based on the positive results obtained with the thesis work of Schade (15) and Dorr (17), a new plant for quasi-continuous wet granulation and multiple-chambered fluid-bed drying was developed by Glatt AG CH-Pratteln in cooperation with F. Hoffmann-La Roche Ltd. Basel and the Institute of Pharmaceutical Technology of the University of Basel. 

Compression force/hardness profile The compression/hardness profile of a granule batch is an important property. Different subunits of two formulations were selected and compressed using different compression forces in order to obtain tablets. The tablets were tested for hardness as a function of different subrmit numbers (Figs. 11,12). From experience, it is well known that certain formulations show an excellent compression profile as small batches but do not keep this property on the batch size increasing. This is another advantage of the quasi-continuous production concept as, in principle, the quality of the small batch is not changed by the repetitive procedure. 

Fig. 7.47 Quasi-continuous system for mixing, granulating, and drying featuring a bowl mixer/granulatorwith 600 L bowl volume and external fluidized bed dryer. A schematic of the entire system is shown in the inset (courtesy DIOSNA, Osnabriick, Germany).

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