Life cycle assessment of pharmaceutical tablet manufacturing: A comparative analysis and systems model integration framework

Abstract

Pharmaceutical drug products in the form of tablets are produced via a series of manufacturing steps, transforming powder blends to compacted granules with carefully selected properties such as tensile strength and dissolution time. Typical oral solid dosage form (OSD) manufacturing processes include direct compression (DC), roller compaction (RC), high shear granulation (HSG) and continuous direct compression (CDC). Design of each process step is required to achieve end-product quality for the specific material properties and available equipment, although design decisions are typically made without a quantitative understanding of the impact on product environmental footprint. Using a ‘cradle-to-gate’ life cycle assessment (LCA) methodology, a quantitative sustainability comparison has been made between standard OSD manufacturing platforms across different production scales. The results demonstrate that for small batch sizes, DC produces tablets with the lowest carbon footprint, however at larger batch sizes, CDC is the most carbon efficient manufacturing platform. Due to the high carbon footprint of the active pharmaceutical ingredient (API), formulation process yields had the greatest impact on overall carbon footprint, although emissions from equipment energy, cleaning and facility overheads were also analysed. Data from these LCA models has been combined with systems models of the CDC manufacturing processes. These combined models are used to demonstrate the optimisation of processes to meet robust product quality attribute targets whilst identifying opportunities to minimise the drug product carbon footprint.