Solvent Selection, Sustainability Analysis & Technoeconomic Evaluation and Optimisation of Batch Cooling Crystallisation Processes for Flurbiprofen Production

Selecting suitable solvents for the crystallisation of pharmaceuticals can be a challenging task, given the vast number of solvents that we have to choose from. To simplify this problem, however, we can use principles from solid-liquid equilibria (SLE) alongside established thermodynamic models to identify promising candidates prior to conducting experiments. In light of this, we have studied 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. To achieve this, we have used the Apelblat equation to describe the thermophysical behaviour of flurbiprofen across a wide range of temperatures (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). Meanwhile, we have used green metrics (e.g., E-factor, Scope 1 and 2 carbon emissions) alongside established process economics models to determine the solvent which is most likely to result in an environmentally friendly and low-cost process (n-propanol).