Robust Techno-economic Analysis, Life Cycle Assessment, and Quality and Sustainability by Digital Design of Three Alternative Continuous Pharmaceutical Tablet Manufacturing Processes

This study presents a comprehensive comparison of the three alternative downstream manufacturing technologies for pharmaceuticals: i) Dry Granulation (DG) through roller compaction, ii) Direct Compaction (DC), and iii) Wet Granulation (WG) based on the economic, environmental and product quality performances. Firstly, the integrated dynamic mathematical models of the different downstream (drug product) processes were developed using gPROMS formulated products based on data from the literature or/and our recent experimental work. The process models were developed and simulated to reliably capture the impact of the different design options, process parameters, and material attributes. Uncertainty analysis was conducted using global sensitivity analysis to identify the set of critical process parameters (CPP) and critical material attributes (CMA) that mostly influence the quality and performance of the final pharmaceutical tablets in each case, captured by the critical quality attributes (CQAs). Based on the set of CPP and CMA, the combined design spaces, which guarantee the attainment of the targeted CQA, were identified and compared. Additionally, based on the process simulations results and inventory data, the techno-economic Analysis was performed alongside life cycle assessment (LCA). The LCA provided an in-depth evaluation of the environmental impacts associated with each manufacturing method, considering aspects such as energy consumption, raw material usage, emissions, and waste generation based on a cradle-to-gate approach. By integrating the CQAs and critical emission categories within a Quality and and Sustainability by Digital Design (QSbDD) paradigm, this study offers a holistic analysis that captures both the environmental and product quality performance.