Pellet layering: scale-up considerations using different kinds of processing equipment.

OBJECTIVE

In this study an aqueous suspension of poorly water-soluble HCT (hydrochlorothiazide) was layered on small spherical starter cores with a drug content in the final pellets of 30%. The aim was to compare different kinds of processing equipment (Wurster fluid-bed, CPS rotor fluid-bed and drum coater) in view of process efficiency, process duration and feasibility to scale-up.

RESULTS

In a pilot scale drum coater, it was possible to achieve the desired LE (layering efficiency) and yield specifications (both >95%), but the process duration was at least 202 min. In the small scale Wurster fluid-bed machine, it was possible to reduce the process time for an optimized process from 67 min to 41 min. However, the acceleration of the process led to an increase of agglomerates and the same process took at least 114 min in the scale-up experiments. A small scale CPS rotor processor with a cone-shaped disc was superior to the conventional planar rotor disc design, regarding yield and agglomerates. This rotor process was both, fast and highly efficient (yield: 98.4%; LE: 99.3%). The high quality of the process was also observed for the pilot scale batches, in which neither considerable losses of drug (LE ≥ 98.6%) nor formation of agglomerates occurred. The absolute spray rate in this pilot scale process was 85 kg/h.

CONCLUSION

Best results were achieved with the CPS rotor technology. With a duration of 29 min (small scale) and 44 min (pilot scale) it was the fastest option to produce layered pellets.