Continuous Wet Granulation

Abstract

Wet granulation is a critical unit operation in solid dosage form manufacturing in the pharmaceutical industry. Traditionally, wet granulation has been a batch process. Recently, there has been a move toward more advanced manufacturing approaches such as continuous processing to allow more rigorous process control, consistent quality assurance, and reduced capital costs. This chapter discusses continuous wet granulation process with emphasis on twin screw granulation as the most commonly used continuous granulation approach in the pharmaceutical industry. The key design features of a twin screw granulator (TSG) are described, and comparisons with batch high shear granulation equipment are made. The effects of formulation and process variables on granule attributes are discussed. Mechanistic studies of screw elements with the proposed granulation rate processes are presented. Real-time process monitoring tools, including spectroscopic and imaging techniques, are described. Implementation of dimensional analysis as a tool for scaling up/scaling out of continuous twin screw granulation is presented. Two numerical methods, that is, population balance model (PBM) and discrete element method (DEM), are chosen for the multiscale modeling of twin screw granulation, and their coupling mechanisms of data exchange between DEM and PBM are discussed.