ABSTRACT
We report here a fully automated, end-to-end, integrated continuous manufacturing process for a small-molecule generic medication with built-in quality assurance. The entire process fits into a box of 30.7 m2 modular footprint and a total residence time of less than 30 h, with a throughput up to 40.3 × 106 tablets per year.
Subject(s)
Drug Industry/methods , Pharmaceutical Preparations/chemical synthesis , Drug Industry/instrumentationABSTRACT
As twin screw granulation (TSG) provides one with many screw element options, characterization of each screw element is crucial in optimizing the screw configuration in order to obtain desired granule attributes. In this study, the performance of two different screw elements - distributive feed screws and kneading elements - was studied in an 11 mm TSG at different liquid-to-solid (L/S) ratios. The kneading element configuration was found to break large granules more efficiently, leading to narrower granule size distributions. While pharmaceutical industry shifts toward continuous manufacturing, inline monitoring and process control are gaining importance. Granules from an 11 mm TSG were analysed using the Eyecon™, a real-time high speed direct imaging system, which has been used to capture accurate particle size distribution and particle count. The size parameters and particle count were then assessed in terms of their ability to be a suitable control measure using the Shewhart control charts. d10 and particle count were found to be good indicators of the change in L/S ratio. However, d50 and d90 did not reflect the change, due to their inherent variability even when the process is at steady state.
