Continuous Twin Screw Wet Granulation: A Step towards Mechanistic Understanding

Twin screw granulation is the most recent technique used for continuous wet granulation across the pharmaceutical industry.The research works published so far are pioneering but more work needs to be done to bring twin screw granulation from a developing state to a fully industrialised and commercialised state in the pharmaceutical industry.Currently, one of the main challenges and deterring issues in twin screw granulation is the limited control on granule attributes (size, amount of small and large granules etc.) owing to the limited mechanistic understanding of granulation process.For an instance, TSG generally produces granules with bimodal, wide size distribution, which is often not desirable during tabletting as it can lead to variability in the tablet attributes.This requires milling of oversize granules resulting in increase in process time, cost and potentially production of more fines.Such bimodal size distribution from TSG has to be turned into monomodal and narrow granules size distribution.Hence, there is a need to address such challenges to increase the acceptability of the twin screw granulation as an efficient continuous wet granulation technique.Therefore, in this research work an attempt was made to develop a thorough mechanistic understanding of twin screw wet granulation process with respect to effects of various formulation (L/S, type of powders) and process (type of screw element, screw configuration, screw speed, powder feed rate, fill level, barrel temperature) variables on the granule properties such as size, shape and structure and tablet tensile strength.Increasing number of kneading elements the granule become bigger in size, elongated, smoother and denser due to coalescence and consolidation (as result of higher shear and compaction stresses acting on granules).However, addition of conveying elements after kneading elements in the screw configuration resulted in decrease in granule size and elongation, due to cutting and chopping action of the conveying elements.As L/S increased above critical level (which is L/S-0.1 in case of lactose) the granule size increased.It was also found that, material property plays more important role while studying fill level.Lactose powder maintained granule size at changing barrel fill levels (SFL and PFN).