Towards Sustainable Practices in Pharmaceutical Research and Development: A Life Cycle Approach

Abstract

This project is an environmental impact and cost analysis of commonly used crystallization processes for isolating and purifying active pharmaceutical ingredients (APIs) at Solid State Pharma Inc., a pharmaceutical research organization. A comprehensive Life Cycle Inventory (LCI) has been compiled for cooling, antisolvent, evaporative, and reactive crystallization processes, covering aspects from raw material extraction to waste disposal, providing a cradle-to-gate evaluation for the API and a cradle-to-grave evaluation for the solvent. Relevant environmental impact categories such as global warming potential, fossil fuel potential, and human toxicity potential have been considered to quantify environmental burdens across the life cycle stages. A comparison between solvent recycling and incineration scenarios has been made to evaluate environmental impacts.

The project's main objective was to identify resource consumption hotspots in these crystallization processes. This was achieved by compiling a detailed LCI for selected processes and developing a life cycle model for environmental impact assessment. Among the processes investigated, reactive crystallization proves most prevalent (38.9%), followed by antisolvent processes (25.9%), while evaporative and cooling processes showed similar occurrence rates.

Solvent usage analysis revealed that water was the most prevalent solvent (22.6% usage), with class 3 solvents predominating (74.1% usage). Reactive and evaporative processes tended to use higher solvent amounts compared to other types, though some reactive processes exhibited lower solvent usage akin to cooling processes. Dichloromethane emerged as a significant class 2 solvent, notably present in process P32, which constituted 75% of the total amount used in all processes.

Environmental impact assessment indicated that solvent production was the primary contributor in the incineration option. However, implementing solvent recovery systems significantly reduced these impacts, making the recovery option more environmentally favourable. Economic analysis showed that operating costs are predominantly associated with solvent procurement, with cooling crystallization generally exhibiting the lowest costs due to reduced solvent usage. Further, solvent recovery systems showed high returns on investment at larger production scales, suggesting their viability for cost savings and profitability.

Overall, the project provided valuable insights into the environmental and economic implications of different crystallization processes, emphasizing the importance of solvent choice and recovery systems in pharmaceutical manufacturing. It laid the groundwork for developing expert systems for comparative assessments of crystallization technologies, furthering environmental sustainability and cost-effectiveness in the pharmaceutical industry.