Comparison of a continuous ring layer wet granulation process with batch high shear and fluidized bed granulation processes

Abstract

The traditional batch wet granulation processes encounter several challenges, such as problems in the scale-up step, batch-to-batch variability together with the multivariate and difficult to control nature of the process. A continuous wet granulation technique could be a possible solution for the scale-up problem, offering adjustable production volumes with the same equipment. In this study, a continuous ring layer wet granulation process (factors: shaft speed and binder flow rate) was compared with two batch granulation processes: high shear (factors: impeller speed and chopper speed) and fluidized bed (factors: inlet air temperature during granulation and binder flow rate) with formulations consisting of paracetamol, microcrystalline cellulose and polyvinylpyrrolidone. A quantitative PLS model was formed to assess the effects of the process parameters on the granule properties (the mean granule size and flowability). In the case of the continuous ring layer granulation process, the mean granule size increased linearly with increasing shaft speed and binder flow rate, and the granules resembled morphologically more the granules produced by the high shear granulation than by the fluidized bed granulation. It is notable that the continuous ring layer granulation process was easier to control than the fluidized bed and high shear granulation processes due to the linear responses towards changes in operation conditions. Both types of tablets, compressed either from the granules produced by the continuous ring layer granulation or by the high shear granulation, achieved an immediate drug release. In summary, the continuous ring layer granulation process was demonstrated to represent a promising tool for the production of pharmaceutical granules.