Abstract
Identifying cost-optimal yet environmentally friendly crystallisation processes in the production of small molecule pharmaceuticals is a highly complex task, since multiple solvent systems often exist which could be used to purify a given drug to a similar standard. It is, however, rarely possible to test each of these solvent systems within a laboratory setting, since this would be time-consuming and incur large material costs. It has, therefore, been suggested that process modelling tools should be used to screen different crystallisation processes available to produce a new drug prior to studying them experimentally - essentially allowing a shortlist of promising process candidates to be created. Indeed, it has been shown by several authors that this sort of work can be conducted without any need to establish the crystallisation kinetics associated with each drug-and-solvent combination considered: the reason being that crystallisation processes may be defined as simple solid-liquid equilibria (SLE) problems using thermodynamic models alone. Considering this, the present work has used SLE modelling to assess the cost and environmental impact of different solvent systems available for the crystallisation of pregabalin - an anticonvulsant and anxiolytic drug used to treat epilepsy, anxiety and neuropathic pain. Moreover, it has used entirely data-led approaches to achieve this: leveraging established costing methodologies and green metrics (i.e., Scope 1 and 2 CO2e emissions) to assess their economic viability and carbon footprint. This modelling framework can be used to identify viable crystallisation strategies for other small molecules.