Experience with the Diosna mini-granulator and assessment of process scalability.

ABSTRACT

A small-scale appliance for the high-shear granulation of pharmaceutical materials (the Diosna P 1-6) was tested in a study investigating the influence of various granulation parameters and formulations on granule size distribution. Increasing the granulation time, the impeller speed and the amount of binder all resulted in an increase in granule size, whilst high fill ratios resulted in an increased proportion of fines. The speed of the chopper did not affect granule size distribution for the formulations tested. Granule size distribution was highly reproducible within individual bowl sizes. Scale-up to the P 10 granulator could be accomplished without changing the formulation or the granulation conditions providing that the different bowl sizes of the laboratory-scale equipment yielded granulates with comparable size distributions. Further scale-up to Diosna P 25 and P 100 granulators, which are larger scale machines, resulted in granules which were smaller than those prepared in the laboratory-scale equipment. The Diosna P 1-6 seems to be a useful tool for experimentation carried out in the early phase of pharmaceutical development work. Granulates can be prepared reproducibly and differences in granule size distribution due to machine scale can be assessed.