Abstract
Choosing suitable solvents for crystallisation processes can be a challenging task when developing new pharmaceuticals, given the vast number of candidates available. To streamline this task, however, process modelling tools can be used to systematically probe the behaviour of different crystallisation setups entirely in-silico. In fact, it is possible to couple thermodynamic models with basic solid-liquid equilibria (SLE) principles to determine the impact of key process variables (e.g., temperature and solvent choice) on process performance, prior to conducting lab-scale experiments. In light of this, in this study we have used thermodynamic computational modelling tools (implemented within MATLAB®) to evaluate the cost and environmental impact of different batch crystallisation processes that may be used to manufacture flurbiprofen – a non-steroidal anti-inflammatory drug (NSAID) that can be used to treat various forms of arthritis. To complete this work, we have used the Apelblat equation to study the solubility of flurbiprofen in four (4) common solvents (n-octane, methyl tert-butyl ether, n-propanol, and isopropyl acetate) over a wide temperature range (283.15-323.15 K). Further to this, we have used green metrics (i.e., E-factor) and established costing methodologies to compare each process candidate; before evaluating their Scope 1 and 2 CO2e emissions by considering their electricity usage and incineration activities.