Solvent selection, sustainability analysis, technoeconomic evaluation and optimisation of batch cooling crystallisation for flurbiprofen production

Selecting suitable solvents for the crystallisation of pharmaceuticals can be a challenging task, given the vast number of solvents that we can choose from. To simplify this problem, we can use principles from solid-liquid equilibria (SLE) alongside established thermodynamic models to identify promising candidates prior to conducting experiments. This study addresses the batch cooling crystallisation of flurbiprofen – a non-steroidal anti-inflammatory drug (NSAID) used to treat arthritis – using a simple model framework implemented within MATLAB. The Apelblat equation is employed to describe the thermophysical behaviour of flurbiprofen over a wide temperature range (283.15–323.15 K) in twelve (12) solvents: three alkanes (n-hexane, n-heptane, n-octane); two (isopropyl, methyl-tert-butyl) ethers; five alcohols (n-propanol, isopropanol, n-butanol, isobutanol, isopentanol); an ester (isopropyl acetate); and a nitrile (acetonitrile). Moreover, we have used green metrics (E-factor, Scope 1 and 2 carbon emissions) with established process economics models to determine the most promising solvent (n-propanol) for an environmentally friendly and economical manufacturing process.