An Integrated Approach to Simulation of Pharmaceutical Processes for Solid Drug Manufacture

There are significant economic incentives to transition from batch to continuous processing of pharmaceutical products. However, several challenges must be overcome in order to implement continuous manufacturing systems for solids-based processes. Among these is the need to develop increased understanding of continuous processes and their sensitivity to variability in input materials, processing equipment, and operating conditions. In the current work, integrated flowsheet modeling is used to evaluate a continuous process for tablet production via direct compaction. Simulation of the flowsheet model is used to assess the impact of variability in input material properties as well as process design and operating parameters on product quality. Global sensitivity analysis is also used to identify gaps in the existing process model with the goal of determining specific areas where model improvement can be effected.